Gene Summary

Gene:CD24; CD24 molecule
Aliases: CD24A
Summary:This gene encodes a sialoglycoprotein that is expressed on mature granulocytes and B cells and modulates growth and differentiation signals to these cells. The precursor protein is cleaved to a short 32 amino acid mature peptide which is anchored via a glycosyl phosphatidylinositol (GPI) link to the cell surface. This gene was missing from previous genome assemblies, but is properly located on chromosome 6. Non-transcribed pseudogenes have been designated on chromosomes 1, 15, 20, and Y. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2014]
Databases:VEGA, OMIM, HGNC, Ensembl, GeneCard, Gene
Protein:signal transducer CD24
Source:NCBIAccessed: 16 March, 2017


What does this gene/protein do?
Show (36)

Cancer Overview

Research Indicators

Publications Per Year (1992-2017)
Graph generated 16 March 2017 using data from PubMed using criteria.

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

Tag cloud generated 16 March, 2017 using data from PubMed, MeSH and CancerIndex

Specific Cancers (7)

Data table showing topics related to specific cancers and associated disorders. Scope includes mutations and abnormal protein expression.

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Latest Publications: CD24 (cancer-related)

Onishi H, Suyama K, Yamasaki A, et al.
CD24 Modulates Chemosensitivity of MCF-7 Breast Cancer Cells.
Anticancer Res. 2017; 37(2):561-565 [PubMed] Related Publications
The role of cluster of differentiation (CD) 24 in breast cancer remains unclear; previously, we showed that CD24 suppresses malignant phenotypes by inactivating Hedgehog signaling through signal transducer and activator of transcription (STAT) 1 inhibition. In this study, we examined how CD24 affects chemosensitivity in breast cancer cells. The CD44(+)CD24(+) breast cancer cell line MCF-7 was transfected with CD24 with/without STAT1 siRNA, and chemosensitivity to 5-fluorouracil (5-FU) and cis-diamminedichloroplatinum (CDDP) was measured. CD24 inhibition reduced chemosensitivity to 5-FU, while STAT1 inhibition did not affect chemosensitivity to 5-FU in CD24 siRNA-transfected cells. Conversely, CD24 inhibition did not affect chemosensitivity to CDDP, while STAT1 inhibition reduced chemosensitivity to CDDP in CD24 siRNA-transfected cells. STAT1 inhibition, but not CD24 inhibition, reduced expression of the ATP-binding cassette (ABC) transporter genes, ABCB1 and ABCG2. In conclusion, CD24 inhibition may modulate chemosensitivity according to drug type, but ABC transporter expression appears not to contribute to this mechanism. This study contributes to determining the role of CD24 in breast cancer.

Roudi R, Madjd Z, Ebrahimi M, et al.
Evidence for embryonic stem-like signature and epithelial-mesenchymal transition features in the spheroid cells derived from lung adenocarcinoma.
Tumour Biol. 2016; 37(9):11843-11859 [PubMed] Related Publications
Identification of the cellular and molecular aspects of lung cancer stem cells (LCSCs) that are suggested to be the main culprit of tumor initiation, maintenance, drug resistance, and relapse is a prerequisite for targeted therapy of lung cancer. In the current study, LCSCs subpopulation of A549 cells was enriched, and after characterization of the spheroid cells, complementary DNA (cDNA) microarray analysis was applied to identify differentially expressed genes (DEGs) between the spheroid and parental cells. Microarray results were validated using quantitative real-time reverse transcription-PCR (qRT-PCR), flow cytometry, and western blotting. Our results showed that spheroid cells had higher clonogenic potential, up-regulation of stemness gene Sox2, loss of CD44 expression, and gain of CD24 expression compared to parental cells. Among a total of 160 genes that were differentially expressed between the spheroid cells and the parental cells, 104 genes were up-regulated and 56 genes were down-regulated. Analysis of cDNA microarray revealed an embryonic stem cell-like signature and over-expression of epithelial-mesenchymal transition (EMT)-associated genes in the spheroid cells. cDNA microarray results were validated at the gene expression level using qRT-PCR, and further validation was performed at the protein level by flow cytometry and western blotting. The embryonic stem cell-like signature in the spheroid cells supports two important notions: maintenance of CSCs phenotype by dedifferentiating mechanisms activated through oncogenic pathways and the origination of CSCs from embryonic stem cells (ESCs). PI3/AKT3, as the most common up-regulated pathway, and other pathways related to aggressive tumor behavior and EMT process can confer to the spheroid cells' high potential for metastasis and distant seeding.

Ma X, Zhang Y, Kang Y, et al.
A recombinant protein TmSm(T34A) can inhibit proliferation and proapoptosis to breast cancer stem cells(BCSCs) by down-regulating the expression of Cyclin D1.
Biomed Pharmacother. 2016; 84:373-381 [PubMed] Related Publications
Cancer stem cells (CSCs), a small fraction of cancer cells lines proved with stem cell characteristics, were regarded as "bad seeds" related to recurrence, metastasis and chemotherapy resistance of breast carcinoma in recent years. So inhibiting the growth or inducing the differentiation and apoptosis of CSCs were considered as one of the effective pathways to fight against breast cancer. Based on the recombinant protein TmSm(T34A) that was designed and prepared in our previous experiments for targeting survivin, an inhibitor of apoptosis protein(IAP), in this study, we explored the effects of TmSm(T34A) on BCSCs obtained by enriching in serum-free suspension, sorting and characterizing of MCF-7/ADM. The results showed that TmSm(T34A) could not only inhibit the proliferation and growth of BCSCs by decreasing CD44(+)CD24(-) proportion and down-regulating the expression of Cyclin D1 significantly, but also induce BCSCs apoptosis evidently. Furthermore, in BCSCs xenograft nude mice administrated TmSm(T34A), the tumor growth was slower than that of the control obviously. Thus it can be seen TmSm(T34A) would be a promising potential protein for treatment of breast cancer by effecting on BCSCs.

Tang X, Li X, Li Z, et al.
Downregulation of CXCR7 inhibits proliferative capacity and stem cell-like properties in breast cancer stem cells.
Tumour Biol. 2016; 37(10):13425-13433 [PubMed] Related Publications
Breast cancer stem cells (bCSCs) are considered an obstacle in breast cancer therapy because they exhibit long-term proliferative potential, phenotypic plasticity and high resistance to the current therapeutics. CXC chemokine receptor type 7 (CXCR7), which provides a growth advantage to breast cancer cells, has recently been demonstrated to play an important role in the maintenance of stem cell-like properties in the CSCs of glioblastoma and lung cancer, yet its role in bCSCs remains elusive. In this study, CD44(+)/CD24(low) bCSC-enriched cells (bCSCs for short) were isolated from MCF-7 cells, and CXCR7 was stably knocked down in bCSCs via lentivirus-mediated transduction with CXCR7 short hairpin RNA (shRNA). Knockdown of CXCR7 in bCSCs decreased the proportion of CD44(+)/CD24(low) cells, and markedly reduced the clonogenicity of the cells. Moreover, silencing of CXCR7 downregulated the expression of stem cell markers, such as aldehyde dehydrogenase 1 (ALDH1), Oct4, and Nanog. In addition, CXCR7 silencing in bCSCs suppressed cell proliferation and G1/S transition in vitro, and delayed tumor growth in vivo in a xenograft mouse model. In situ immunohistochemical analysis revealed a reduction in Ki-67 expression and enhanced apoptosis in the xenograft tumors as a result of CXCR7 silencing. Furthermore, combined treatment with CXCR7 silencing and epirubicin displayed an outstanding anti-tumor effect compared with either single treatment. Our study demonstrates that CXCR7 plays a critical role in the maintenance of stem cell-like properties and promotion of growth in bCSCs, and suggests that CXCR7 may be a candidate target for bCSCs in breast cancer therapy.

Eterno V, Zambelli A, Villani L, et al.
AurkA controls self-renewal of breast cancer-initiating cells promoting wnt3a stabilization through suppression of miR-128.
Sci Rep. 2016; 6:28436 [PubMed] Free Access to Full Article Related Publications
AurkA overexpression was previously found in breast cancer and associated to its ability in controlling chromosome segregation during mitosis, however whether it may affect breast cancer cells, endorsed with stem properties (BCICs), is still unclear. Surprisingly, a strong correlation between AurkA expression and β-catenin localization in breast cancer tissues suggested a link between AurkA and Wnt signaling. In our study, AurkA knock-down reduced wnt3a mRNA and suppressed metastatic signature of MDA-MB-231 cells. As a consequence, the amount of BCICs and their migratory capability dramatically decreased. Conversely, wnt3a mRNA stabilization and increased CD44(+)/CD24(low/-) subpopulation was found in AurkA-overexpressing MCF7 cells. In vivo, AurkA-overexpressing primary breast cancer cells showed higher tumorigenic properties. Interestingly, we found that AurkA suppressed the expression of miR-128, inhibitor of wnt3a mRNA stabilization. Namely, miR-128 suppression realized after AurkA binding to Snail. Remarkably, a strong correlation between AurkA and miR-128 expression in breast cancer tissues confirmed our findings. This study provides novel insights into an undisclosed role for the kinase AurkA in self-renewal and migration of BCICs affecting response to cancer therapies, metastatic spread and recurrence. In addition, it suggests a new therapeutic strategy taking advantage of miR-128 to suppress AurkA-Wnt3a signaling.

Wu H, Zhang J, Shi H
Expression of cancer stem markers could be influenced by silencing of p16 gene in HeLa cervical carcinoma cells.
Eur J Gynaecol Oncol. 2016; 37(2):221-5 [PubMed] Related Publications
Effect of the tumor suppression gene p16 on the biological characteristics of HeLa cervical carcinoma cells was explored. The expression of p16 protein was increased in HeLa tumor sphere cells, and no significant difference in tumor spheres from the first to the fourth passages. Compared with those of parental HeLa cells, the proportion of CD44+/CD24- and ABCG2+ cells increased significantly in tumor spheres. However after the cells were silenced by the p16-sh289 vector, expression of P16 protein and the cell number of CD44+/CD24- and ABCG2+ decreased. Moreover, HeLa cells with p16 gene silencing showed decreased abilities of sphere formation and matrigel invasion. More HeLa cells with p16 gene silence were needed for tumor formation in nude mice. Tumor size and weight in mouse model established with p16 gene silenced HeLa cells were less than those with HeLa parental cell model. The present results indicate that silencing of the p16 gene inhibits expression of cancer stem cell markers and tumorigenic ability of HeLa cells.

Han ML, Wang F, Gu YT, et al.
MicroR-760 suppresses cancer stem cell subpopulation and breast cancer cell proliferation and metastasis: By down-regulating NANOG.
Biomed Pharmacother. 2016; 80:304-10 [PubMed] Related Publications
BACKGROUND AND OBJECTIVE: Emerging evidences suggest that cancer stem cells are responsible for tumor aggressive, metastasis and therapeutic resistance. To data, the mechanism underlying breast cancer stem cell (BCSC) population within tumor metastasis remains to be fully elucidated. The current study was to investigate the potential role of microRNA-760 (miR-760) and its associated target gene in population and metastasis of BCSC.
METHODS: Characteristic BCSCs surface markers (CD44(+)/CD24(-/low)) were determined by flow cytometry in breast cancer MCF-7 and BT-549 cells. Quantitative RT-PCR was used to evaluate miR-760 and NANOG mRNA expression. Expression of NANOG protein was determined using western blot. Cell proliferation was determined by MTT assay. The model of breast cancer cell xenograft was used to evaluate the effect of miR-760 on tumor growth.
RESULTS: BT-549 cell has substantially more CD44(+)/CD24(-/low) subpopulation than MCF-7 cell. Moreover, BT-549 cell expressed lower level of miR-760 and higher level of NANOG than MCF-7cell. By result from cellular miR-760 modulation, we found that miR-760 overexpression suppressed CD44(+)/CD24(-/low) population as well as inhibited cell proliferation and migration of BT-549. On the contrary, knockdown of miR-760 promoted CD44(+)/CD24(-/low) population and migration of MCF-7 cells. By luciferase reporter assay, miR-760 was proved to be functional associated with NANOG via regulating its expression. This functional interaction was showed to be involved in controlling proliferation and migration of MCF-7 and BT-549 cell.
CONCLUSION: These data suggest that the target of miR-760/NANOG axis may represent a new therapeutic approach to suppress breast cancer stem cell subpopulation thereby prevent cancer metastasis.

Kim SH, Kaschula CH, Priedigkeit N, et al.
Forkhead Box Q1 Is a Novel Target of Breast Cancer Stem Cell Inhibition by Diallyl Trisulfide.
J Biol Chem. 2016; 291(26):13495-508 [PubMed] Article available free on PMC after 24/06/2017 Related Publications
Diallyl trisulfide (DATS), a metabolic byproduct of garlic, is known to inhibit the growth of breast cancer cells in vitro and in vivo This study demonstrates that DATS targets breast cancer stem cells (bCSC). Exposure of MCF-7 and SUM159 human breast cancer cells to pharmacological concentrations of DATS (2.5 and 5 μm) resulted in dose-dependent inhibition of bCSC, as evidenced by a mammosphere assay and flow cytometric analysis of aldehyde dehydrogenase 1 (ALDH1) activity and the CD44(high)/CD24(low)/epithelial specific antigen-positive fraction. DATS-mediated inhibition of bCSC was associated with a decrease in the protein level of FoxQ1. Overexpression of FoxQ1 in MCF-7 and SUM159 cells increased ALDH1 activity and the CD49f(+)/CD24(-) fraction. Inhibition of ALDH1 activity and/or mammosphere formation upon DATS treatment was significantly attenuated by overexpression of FoxQ1. In agreement with these results, stable knockdown of FoxQ1 using small hairpin RNA augmented bCSC inhibition by DATS. Expression profiling for cancer stem cell-related genes suggested that FoxQ1 may negatively regulate the expression of Dachshund homolog 1 (DACH1), whose expression is lost in invasive breast cancer. Chromatin immunoprecipitation confirmed recruitment of FoxQ1 at the DACH1 promoter. Moreover, inducible expression of DACH1 augmented DATS-mediated inhibition of bCSC. Expression of FoxQ1 protein was significantly higher in triple-negative breast cancer cases compared with normal mammary tissues. Moreover, an inverse association was observed between FoxQ1 and DACH1 gene expression in breast cancer cell lines and tumors. DATS administration inhibited ALDH1 activity in vivo in SUM159 xenografts. These results indicate that FoxQ1 is a novel target of bCSC inhibition by DATS.

Kim MH, Kim MH, Kim KS, et al.
In vivo monitoring of CD44+ cancer stem-like cells by γ-irradiation in breast cancer.
Int J Oncol. 2016; 48(6):2277-86 [PubMed] Article available free on PMC after 24/06/2017 Related Publications
There is increasing evidence that cancer contains cancer stem cells (CSCs) that are capable of regenerating a tumor following chemotherapy or radiotherapy. CD44 and CD133 are used to identify CSCs. This study investigated non-invasive in vivo monitoring of CD44-positive cancer stem-like cells in breast cancer by γ-irradiation using molecular image by fusing the firefly luciferase (fLuc) gene with the CD44 promoter. We generated a breast cancer cell line stably expressing fLuc gene by use of recombinant lentiviral vector controlled by CD44 promoter (MCF7-CL). Irradiated MCF7-CL spheres showed upregulated expression of CD44 and CD133, by immunofluorescence and flow cytometry. Also, gene expression levels of CSCs markers in irradiated spheres were clearly increased. CD44+ CSCs increased fLuc expression and tumor growth in vivo and in vitro. When MCF7-CL was treated with siCD44 and irradiated, CD44 expression was inhibited and cell survival ratio was decreased. MCF7-CL subsets were injected into the mice and irradiated by using a cobalt-60 source. Then, in vivo monitoring was performed to observe the bioluminescence imaging (BLI). When breast cancer was irradiated, relative BLI signal was increased, but tumor volume was decreased compared to non-irradiated tumor. These results indicate that increased CD44 expression, caused by general feature of CSCs by irradiation and sphere formation, can be monitored by using bioluminescence imaging. This system could be useful to evaluate CD44- expressed CSCs in breast cancer by BLI in vivo as well as in vitro for radiotherapy.

Shaikh MV, Kala M, Nivsarkar M
CD90 a potential cancer stem cell marker and a therapeutic target.
Cancer Biomark. 2016; 16(3):301-7 [PubMed] Related Publications
Cancer Stem Cells (CSCs) have been recently identified and their role in carcinogenesis has been ascertained. CSCs have been correlated with high relapse in certain cancers, multiple drug resistance against chemotherapy and metastasis. Several markers such as CD133, CD24, CD44, EpCAM, and CD26 have been identified to isolate and characterize CSCs. None of these markers or their combinations are universal in nature and can be used to isolate CSCs from all types of cancer. CD90 is one such marker whose expression has been extensively studied in recent years. CD90+ cells have been isolated from several types of tumors and shown to exhibit cardinal properties of CSCs such as proliferation, differentiation, spheroid formation, metastasis and ability to form tumor xenograft in immunodeficient mice. It is also found to be co-expressed with several other CSC markers. CD90 is therefore, suggested as a candidate marker as well as a potential therapeutic target for elimination of CSCs.

Li B, Lu Y, Wang H, et al.
miR-221/222 enhance the tumorigenicity of human breast cancer stem cells via modulation of PTEN/Akt pathway.
Biomed Pharmacother. 2016; 79:93-101 [PubMed] Related Publications
BACKGROUND: The miR-221/222 cluster has been discovered to function as oncogene in human malignancies including breast cancer. However, the role of miR-221/222 in the self-renewal of breast cancer stem cells (BCSCs) is not fully understood. In this study, we examined the impact and mechanism of miR-221/222 on the breast cancer cell viability, migration and invasion, and propagation of BCSCs.
METHODS: Human breast cancer cell line MCF-7 was transfected with miR-221/222 mimics or inhibitors to overexpress or knock down miR-221/222 respectively using Lipofactamine 2000. The biological effects of miR-221 and miR-222 were then assessed by cell proliferation assay, colony formation assay and transwell chamber assays. CD44/CD24 staining and mammosphere formation assay were performed to evaluate the ability of BCSCs self-renewal. Potential target gene phosphatase and tensin homolog (PTEN) and its downstream effector, phosphorylated Akt (p-Akt) were identified by Western blot and qRT-PCR methods.
RESULTS: PTEN, a tumor suppressor gene, was confirmed as a target of miR-221/222 in breast cancer cell line MCF-7. Downregulation of PTEN by miR-221/222 increased the phosphorylation of Akt. Enforced expression of miR-221/222 promoted breast cancer cell proliferation, migration and invasion via targeting PTEN/Akt pathway. Importantly, ectopic expression of miR-221/222 enriched the proportion of CD44(+)/CD24(-) BCSCs and improved the mammosphere formation capacity through targeting PTEN/Akt pathway. Blocking the endogenous miR-221/222 restored PTEN expression and subsequently decreased Akt phosphorylation, and thereby reversed this phenotype.
CONCLUSIONS: Our results suggested that miR-221/222 enhance breast cancer growth, migration and invasion, meanwhile propagate the self-renewal of BCSCs. This is achieved possibly through targeting PTEN/Akt pathway. miR-221/222 might be a novel therapeutic candidate for human breast cancer.

Yang N, Zhou TC, Lei XX, et al.
Inhibition of Sonic Hedgehog Signaling Pathway by Thiazole Antibiotic Thiostrepton Attenuates the CD44+/CD24-Stem-Like Population and Sphere-Forming Capacity in Triple-Negative Breast Cancer.
Cell Physiol Biochem. 2016; 38(3):1157-70 [PubMed] Related Publications
BACKGROUND/AIM: Triple-negative breast cancer (TNBC) represents a particular clinical challenge because these cancers do not respond to endocrine therapy or other available targeted agents. The lack of effective agents and obvious targets are major challenges in treating TNBC. In this study we explored the cytostatic effect of thiazole ring containing antibiotic drug thiostrepton on TNBC cell lines and investigated the molecular mechanism.
METHODS: Cell viability was measured by MTT assay. Cell surface marker was monitored by FCM. Western blot was applied to assess the protein expression levels of target genes.
RESULTS: We found that thiostrepton remarkably suppressed the CD44+/CD24- stem-like population and sphere forming capacity of TNBC cell lines. Notably, we showed for the first time that thiostrepton exerted its pharmacological action by targeting sonic hedgehog (SHH) signaling pathway. Thiostrepton repressed SHH ligand expression and reduced Gli-1 nuclear localization in TNBC cell line. Furthermore, the downstream target of SHH signaling undergone dose-dependent, rapid, and sustained loss of mRNA transcript level after thiostrepton treatment. Finally, we showed that SHH ligand was essential for maintaining CD44+/CD24- stem-like population in TNBC cell line.
CONCLUSION: We conclude that thiostrepton suppresses the CD44+/CD24- stem-like population through inhibition of SHH signaling pathway. Our results give a new insight into the mechanism of thiostrepton anti-tumor activity and suggest thiostrepton as a promising agent that targets hedgehog signaling pathway in TNBC.

Ghuwalewala S, Ghatak D, Das P, et al.
CD44(high)CD24(low) molecular signature determines the Cancer Stem Cell and EMT phenotype in Oral Squamous Cell Carcinoma.
Stem Cell Res. 2016; 16(2):405-17 [PubMed] Related Publications
Almost all epithelial tumours contain cancer stem-like cells, which possess a unique property of self-renewal and differentiation. In oral cancer, several biomarkers including cell surface molecules have been exploited for the identification of this highly tumorigenic population. Implicit is the role of CD44 in defining CSCs but CD24 is not well-explored. Here we show that CD44(high)CD24(low) cells isolated from the oral cancer cell lines, not only express stem cell related genes but also exhibit Epithelial-to-Mesenchymal transition (EMT) characteristics. This CD44(high)CD24(low) population gives rise to all other cell types upon differentiation. Typical Cancer Stem Cell (CSC) phenotypes like increased colony formation, sphere forming ability, migration and invasion were also confirmed in CD44(high)CD24(low) cells. Drug transporters were found to be over-expressed in CD44(high)CD24(low) sub-population thereby contributing to elevated chemo-resistance. To validate our findings in-vivo, we determined the relative expression of CD44 and CD24 in clinical samples of OSCC patients. CD44 expression was consistently high whereas CD24 showed significantly lower expression in tumour tissues. Further, the gene expression profile of the CSC and non-CSC population unravels the molecular pathways which may contribute to stemness. We conclude that CD44(high)CD24(low) represents cancer stem-like cells in Oral Squamous Cell Carcinoma.

Jia ZF, Wang LZ, Cao XY, et al.
CD24 genetic variants contribute to overall survival in patients with gastric cancer.
World J Gastroenterol. 2016; 22(7):2373-82 [PubMed] Article available free on PMC after 24/06/2017 Related Publications
AIM: To investigate the role of single nucleotide polymorphisms (SNPs) in CD24 gene in susceptibility and overall survival of gastric cancer (GC).
METHODS: We genotyped 3 tagging SNPs of CD24-P-534 in the promoter region, P170 in the coding region of exon 2 and P1527 in the 3' untranslated region - using polymerase chain reaction-restriction fragment length polymorphism in specimens from 679 histologically-confirmed GC cases, 111 gastric atrophy (GA) cases and 976 tumor-free controls. Serum immunoglobulin G antibodies to Helicobacter pylori (H. pylori) of all subjects were detected by enzyme-linked immunosorbent assay. CD24 expression was evaluated by immunohistochemistry in 131 GC specimens. Correlations between SNPs and risk of GC or GA were shown by P values and odd ratios (ORs) with 95% confidence intervals (95%CI) compared with the most common genotype of each SNP using the unconditional logistic regression model after adjusting for age, sex and H. pylori infection. Survival within each SNP group was plotted by Kaplan-Meier method and compared by log-rank test (recessive model). Hazard ratios with 95%CIs were computed by Cox regression model after adjusting for age, sex, histological type, tumor differentiation, clinical stage and post-operational chemotherapy.
RESULTS: All of the three loci were in Hardy-Weinberg equilibrium in the control group. Median follow-up time for the 600 GC patients included in the survival analysis was 36.2 mo (range, 2.1-66.7 mo; 95%CI: 34.3-36.5 mo). Patients with the P-534 A/A genotype had significantly shorter survival (HR = 1.38, 95%CI: 1.01-1.88, P = 0.042) than did the C/C or C/A genotype carriers after adjusting for age, sex, histological type, tumor differentiation, clinical stage and post-operational chemotherapy. This trend was more evident in patients who lived longer than 2.5 years (HR = 7.55, 95%CI: 2.16-26.32, P = 0.001). The P170 T/T genotype was associated with a shorter lifespan than the non-T/T genotypes, but not significantly so. None of the three genetic variants was found to be associated with risk of GC (including tumor stage, grade and distant metastasis) or with risk of gastric atrophy. Furthermore, no difference of CD24 expression was found among the genotypes.
CONCLUSION: The P-534 site in CD24 gene affects the overall survival of gastric cancer and may serve as a prognostic marker for gastric cancer.

Gradiz R, Silva HC, Carvalho L, et al.
MIA PaCa-2 and PANC-1 - pancreas ductal adenocarcinoma cell lines with neuroendocrine differentiation and somatostatin receptors.
Sci Rep. 2016; 6:21648 [PubMed] Article available free on PMC after 24/06/2017 Related Publications
Studies using cell lines should always characterize these cells to ensure that the results are not distorted by unexpected morphological or genetic changes possibly due to culture time or passage number. Thus, the aim of this study was to describe those MIA PaCa-2 and PANC-1 cell line phenotype and genotype characteristics that may play a crucial role in pancreatic cancer therapeutic assays, namely neuroendocrine chemotherapy and peptide receptor radionuclide therapy. Epithelial, mesenchymal, endocrine and stem cell marker characterization was performed by immunohistochemistry and flow cytometry, and genotyping by PCR, gene sequencing and capillary electrophoresis. MIA PaCa-2 (polymorphism) expresses CK5.6, AE1/AE3, E-cadherin, vimentin, chromogranin A, synaptophysin, SSTR2 and NTR1 but not CD56. PANC-1 (pleomorphism) expresses CK5.6, MNF-116, vimentin, chromogranin A, CD56 and SSTR2 but not E-cadherin, synaptophysin or NTR1. MIA PaCA-1 is CD24(-), CD44(+/++), CD326(-/+) and CD133/1(-), while PANC-1 is CD24(-/+), CD44(+), CD326(-/+) and CD133/1(-). Both cell lines have KRAS and TP53 mutations and homozygous deletions including the first 3 exons of CDKN2A/p16(INK4A), but no SMAD4/DPC4 mutations or microsatellite instability. Both have neuroendocrine differentiation and SSTR2 receptors, precisely the features making them suitable for the therapies we propose to assay in future studies.

He Z, Huang C, Lin G, Ye Y
siRNA-induced TRAF6 knockdown promotes the apoptosis and inhibits the invasion of human lung cancer SPC-A1 cells.
Oncol Rep. 2016; 35(4):1933-40 [PubMed] Article available free on PMC after 24/06/2017 Related Publications
Tumor necrosis factor receptor-associated factor 6 (TRAF6) has been found to be involved in multiple cancers. However, the effect of small interfering RNA (siRNA)‑induced knockdown of TRAF6 on the biological behaviors of cancer cells remains unknown. Thus, the present study aimed to investigate the effect of siRNA-induced knockdown of TRAF6 on the biological behaviors of human lung cancer SPC-A1 cells. The expression of TRAF6 was determined in human lung adenocarcinoma A549, non-small cell lung cancer H1650, human airway epithelial Calu-3 and human lung cancer SPC-A1 cell lines using quantitative RT-PCR (qRT‑PCR) and western blotting at the transcriptional and translational levels. TRAF6 expression was knocked down in the SPC-A1 cells using an siRNA technique, and the effects of TRAF6 knockdown on NF-κB activity, cell proliferation, apoptosis, cell cycle, invasion and migration of the SPC-A1 cells were determined using electrophoretic mobility shift assay (EMSA), cell proliferation assay, flow cytometry, Transwell invasion assay and scratch wound assay. In addition, the protein expression of CD24, CXCR4, MMP1, MMP2, MMP9, TWIST, TIMP-2 and Slug was quantified using western blotting assay. Western blotting and qRT-PCR assays showed upregulation of TRAF6 at both the translational and transcriptional levels in the Calu-3 and SPC-A1 cells, and K63-linked ubiquitination of TRAF6 and constitutive NF-κB activation were detected in the SPC-A1 cells. Knockdown of TRAF6 inhibited the migration and invasion and promoted the apoptosis of the SPC-A1 cells, but had little effect on cell proliferation and the cell cycle. In addition, siRNA-induced TRAF6 knockdown caused a marked reduction in the protein expression of CD24 and CXCR4, but had little effect on MMP-1, MMP-2, MMP-9, Twist, TIMP-2 or Slug expression. The present study demonstrated that TRAF6 is upregulated in human lung cancer cells, and siRNA-induced TRAF6 knockdown inhibits the invasion of lung cancer cells and promotes apoptosis. It is suggested that TRAF6 may be a promising target for the therapy of lung cancer.

Deng W, Gu L, Li X, et al.
CD24 associates with EGFR and supports EGF/EGFR signaling via RhoA in gastric cancer cells.
J Transl Med. 2016; 14:32 [PubMed] Related Publications
BACKGROUND: CD24, a mucin-like membrane glycoprotein, plays a critical role in carcinogenesis, but its role in human gastric cancer and the underlying mechanism remains undefined.
METHODS: The contents of CD24 and epidermal growth factor receptor (EGFR) in gastric cancer cells (SGC-7901 and BGC-823) and non-malignant gastric epithelial cells (GES-1) were evaluated by Western blotting assay. Cellular EGFR staining was examined by immunofluorescence assay. Cell migration rate was measured by wound healing assay. The effects of depletion/overexperssion of CD24 on EGFR expression and activation of EGF/EGFR singaling pathways were evaluated by immunofluorescence, qPCR, Western blotting and flow cytometry techniques. RhoA activity was assessed by pulldown assay. CD24 and EGFR expression patterns in human gastric tumor samples were also investigated by immunohistochemistry staining.
RESULTS: CD24 was overexpressed in human gastric cancer cells. Ectopic expression of CD24 in gastric epithelial cells augmented the expression of EGFR, while knockdown of CD24 in gastric cancer cells decreased the level of EGFR and cell migration velocity. To further explore the mechanisms, we investigated the effect of CD24 expression on EGF/EGFR signaling. We noticed that this effect of CD24 on EGFR expression was dependent on promoting EGFR internalization and degradation. Lower ERK and Akt phosphorylations in response to EGF stimulation were observed in CD24-depleted cells. In addition, we noticed that the effect of CD24 on EGFR stability was mediated by RhoA activity in SGC-7901 gastric cancer cells. Analysis of gastric cancer specimens revealed a positive correlation between CD24 and EGFR levels and an association between CD24 expression and worse prognosis.
CONCLUSION: Thus, these findings suggest for the first time that CD24 regulates EGFR signaling by inhibiting EGFR internalization and degradation in a RhoA-dependent manner in gastric cancer cells.

Kaczorowski A, Hammer K, Liu L, et al.
Delivery of improved oncolytic adenoviruses by mesenchymal stromal cells for elimination of tumorigenic pancreatic cancer cells.
Oncotarget. 2016; 7(8):9046-59 [PubMed] Article available free on PMC after 24/06/2017 Related Publications
Pancreatic ductal adenocarcinoma (PDA) is one of the most aggressive malignancies and has poor therapeutic options. We evaluated improved oncolytic adenoviruses (OAds), in which the adenoviral gene E1B19K was deleted or a TRAIL transgene was inserted. Bone marrow mesenchymal stromal cells (MSCs) served as carriers for protected and tumor-specific virus transfers. The infection competence, tumor migration, and oncolysis were measured in cancer stem cell (CSC) models of primary and established tumor cells and in tumor xenografts. All OAds infected and lysed CSCs and prevented colony formation. MSCs migrated into PDA spheroids without impaired homing capacity. Xenotransplantation of non-infected PDA cells mixed with infected tumor cells strongly reduced the tumor volume and the expression of the proliferation marker Ki67 along with a necrotic morphology. Adenoviral capsid protein was detected in tumor xenograft tissue after intravenous injection of infected MSCs, but not in normal tissue, implying tumor-specific migration. Likewise, direct in vivo treatment correlated with a strongly reduced tumor volume, lower expression of Ki67 and CD24, and enhanced activity of caspase 3. These data demonstrate that the improved OAds induced efficient oncolysis with the OAd-TRAIL as most promising candidate for future clinical application.

Suyama K, Onishi H, Imaizumi A, et al.
CD24 suppresses malignant phenotype by downregulation of SHH transcription through STAT1 inhibition in breast cancer cells.
Cancer Lett. 2016; 374(1):44-53 [PubMed] Related Publications
Hedgehog (Hh) signaling has been found to be activated in breast cancer stem cells (BCSCs). However, the precise role of the BCSCs marker, CD24, remains unclear. Here, we describe a relationship between CD24 and Sonic Hedgehog (SHH), and reveal a role for this relationship in the induction of a malignant phenotype of breast cancer. CD24 siRNA-transfected breast cancer cells (BCCs) demonstrated higher expression of SHH and GLI1, increased anchorage-independent proliferation, and enhanced invasiveness and superior tumorigenicity compared with control. Conversely, CD24 forced-expressing BCCs possessed decreased SHH and GLI1 expression, anchorage-independent proliferation, and invasiveness. Suppression of SHH decreased invasiveness through inhibition of matrix metalloproteinase (MMP)-2 expression, GLI1 expression, anchorage-independent proliferation, tumorigenicity, and tumor volume in vivo in CD24 siRNA transfected BCCs. DNA microarray analysis identified STAT1 as a relationship between CD24 and SHH. CD24 siRNA-transfected BCCs with concurrent STAT1 inhibition exhibited decreased SHH expression, invasiveness, anchorage-independent proliferation, tumorigenicity, and tumor volume in vivo. These results suggest that CD24 suppresses development of a malignant phenotype by down-regulating SHH transcription through STAT1 inhibition. CD24 gene transfer or STAT1 inhibition may represent new effective therapeutic strategies to target refractory breast cancer.

Kong L, Guo S, Liu C, et al.
Overexpression of SDF-1 activates the NF-κB pathway to induce epithelial to mesenchymal transition and cancer stem cell-like phenotypes of breast cancer cells.
Int J Oncol. 2016; 48(3):1085-94 [PubMed] Related Publications
The formation of EMT and EMT-induced CSC-like phenotype is crucial for the metastasis of tumor cells. The stromal cell-derived factor-1 (SDF-1) is upregulated in various human carcinomas, which is closely associated with proliferation, migration, invasion and prognosis of malignancies. However, limited attention has been directed towards the effect of SDF-1 on epithelial to mesenchymal transition (EMT) or cancer stem cell (CSC)-like phenotype formation in breast cancer cells and the related mechanism. In the present study, we screened MCF-7 cells with low SDF-1 expression level for the purpose of evaluating whether SDF-1 is involved in EMT and CSC-like phenotype formation in MCF-7 cells. The pEGFP-N1-SDF-1 plasmid was transfected into MCF-7 cells, and the stably overexpressed SDF-1 in MCF-7 cells was confirmed by real-time PCR and western blot analysis. Colony formation assay, MTT, wound healing assay and Transwell invasion assay demonstrated that overexpression of SDF-1 significantly boosted the proliferation, migration and invasion of MCF-7 cells compared with parental (P<0.05). Flow cytometry analysis revealed a notable increase of CD44+/CD24- subpopulation in SDF-1 overexpressing MCF-7 cells (P<0.001), accompanied by the apparently elevated ALDH activity and the upregulation of the stem cell markers OCT-4, Nanog, and SOX2 compared with parental (P<0.01). Besides, western blot analysis and immunofluorescence assay observed the significant decreased expression of E-cadherin and enhanced expression of slug, fibronectin and vimentin in SDF-1 overexpressed MCF-7 cells in comparison with parental (P<0.01). Further study found that overexpression of SDF-1 induced the activation of NF-κB pathway in MCF-7 cells. Conversely, suppressing or silencing p65 expression by antagonist or RNA interference could remarkably increase the expression of E-cadherin in SDF-1 overexpressed MCF-7 cells (P<0.001). Overall, the above results indicated that overexpression of SDF-1 enhanced EMT by activating the NF-κB pathway of MCF-7 cells and further induced the formation of CSC-like phenotypes, ultimately promoting the proliferation and metastasis of MCF-7 cells. Therefore, SDF-1 may further be assessed as a potential target for gene therapy of breast cancer.

Pei Z, Zhu G, Huo X, et al.
CD24 promotes the proliferation and inhibits the apoptosis of cervical cancer cells in vitro.
Oncol Rep. 2016; 35(3):1593-601 [PubMed] Related Publications
The protein CD24 is a cell surface protein that appears to function as an adhesion molecule; its expression has been shown to correlate with prognosis in a variety of tumors. Herein, we investigated the possible role and mechanism of CD24 in cervical cancer. Our results showed that CD24 was overexpressed in cervical cancer tissues compared with that in the adjacent non‑cancerous tissues by qPCR, immunohistochemistry and western blotting technologies. To explore the possible mechanism of CD24 in cervical cancer, we elucidated the effect of CD24 on the proliferation and apoptosis of cervical cancer HeLa cells and found that a considerable increase in cell proliferation was observed in the HeLa cells with CD24 overexpession. The rate of cell apoptosis was decreased in the HeLa/CD24 cells compared with the HeLa or HeLa/vector cells. Cell apoptosis is closely related with a reduction in mitochondrial membrane potential (ΔΨm) and an increase in intracellular reactive oxygen species (ROS) and calcium ion (Ca2+) concentrations. Our results showed that overexpression of CD24 in the cervical cancer HeLa cells, led to an increase in ΔΨm and a decrease in intracellular ROS and Ca2+ concentrations. Furthermore, we found that CD24 was correlated with dysregulation of the MAPK signaling pathway in cervical cancer tissues in vitro. At the same time, we found that CD24 overexpression affected the expression of p38, JNK2 and c-Jun in vitro. In summary, our results suggest that CD24 is upregulated in cervical cancer tissues and plays its functions by affecting the MAPK signaling pathway in cervical cancer.

Cheung SK, Chuang PK, Huang HW, et al.
Stage-specific embryonic antigen-3 (SSEA-3) and β3GalT5 are cancer specific and significant markers for breast cancer stem cells.
Proc Natl Acad Sci U S A. 2016; 113(4):960-5 [PubMed] Article available free on PMC after 24/06/2017 Related Publications
The discovery of cancer stem cells (CSCs), which are responsible for self-renewal and tumor growth in heterogeneous cancer tissues, has stimulated interests in developing new cancer therapies and early diagnosis. However, the markers currently used for isolation of CSCs are often not selective enough to enrich CSCs for the study of this special cell population. Here we show that the breast CSCs isolated with CD44(+)CD24(-/lo)SSEA-3(+) or ESA(hi)PROCR(hi)SSEA-3(+) markers had higher tumorigenicity than those with conventional markers in vitro and in vivo. As few as 10 cells with CD44(+)CD24(-/lo)SSEA-3(+) formed tumor in mice, compared with more than 100 cells with CD44(+)CD24(-/lo). Suppression of SSEA-3 expression by knockdown of the gene encoding β-1,3-galactosyltransferase 5 (β3GalT5) in the globo-series pathway, led to apoptosis in cancer cells specifically but had no effect on normal cells. This finding is further supported by the analysis of SSEA-3 and the two related globo-series epitopes SSEA4 and globo-H in stem cells (embryonic stem cells and induced pluripotent stem cells) and various normal and cancer cells, and by the antibody approach to target the globo-series glycans and the late-stage clinical trials of a breast cancer vaccine.

Todoroki K, Ogasawara S, Akiba J, et al.
CD44v3+/CD24- cells possess cancer stem cell-like properties in human oral squamous cell carcinoma.
Int J Oncol. 2016; 48(1):99-109 [PubMed] Article available free on PMC after 24/06/2017 Related Publications
Cancer stem cells (CSCs) or cancer stem cell-like cells (CSC-LCs) are a minority population of cells that relate to tumor progression, metastasis and drug resistance. To identify CSC-LCs in oral squamous cell carcinoma (OSCC), we used two OSCC cell lines, SAS and OSC20, and cell surface markers, CD44v3 and CD24. In addition, we examined CD44v3 and CD24 expression immunohistochemically and evaluated the relationship between the expression and clinicopathological parameters in 50 OSCC tissues. In SAS and OSC20, CD44v3+/CD24- cells showed a higher sphere forming ability than the other fractions, i.e., CD44v3+/CD24+, CD44v3-/CD24- and CD44v3-/CD24+ cells. The proportion of CD44v3+/CD24- cells in SAS and OSC20 was 10.7 and 24.1%, respectively. Regarding SAS, CD44v3+/CD24- cells also showed a higher drug resistance for CDDP, 5-FU and cetuximab and expressed higher mRNA levels of CSC property-related genes than the other cell fractions. The tumorigenicity of CD44v3+/CD24- cells was not significantly different from the other fractions in SAS. An immunohistochemical study revealed a significant correlation between CD44v3 expression in the invasive portion and lymph node metastasis. Kaplan Meier analysis revealed cases with CD44v3 expression in the invasive portion tended to show poor overall survival (OS) compared with those without CD44v3, and there was a significant difference in OS between CD44v3+/CD24- and CD44v3-/CD24- immunophenotypes in the invasive portion. In conclusion, the results suggest that the CD44v3+/CD24- cell population displays CSC-LC properties in a human OSCC cell line. Additionally, we present evidence that CD44v3 immunoexpression and CD44v3+/CD24- immunophenotypes could give prognostic information associated with unfavorable clinical outcomes.

Liu J, Chen X, Ward T, et al.
Niclosamide inhibits epithelial-mesenchymal transition and tumor growth in lapatinib-resistant human epidermal growth factor receptor 2-positive breast cancer.
Int J Biochem Cell Biol. 2016; 71:12-23 [PubMed] Related Publications
Acquired resistance to lapatinib, a human epidermal growth factor receptor 2 kinase inhibitor, remains a clinical problem for women with human epidermal growth factor receptor 2-positive advanced breast cancer, as metastasis is commonly observed in these patients. Niclosamide, an anti-helminthic agent, has recently been shown to exhibit cytotoxicity to tumor cells with stem-like characteristics. This study was designed to identify the mechanisms underlying lapatinib resistance and to determine whether niclosamide inhibits lapatinib resistance by reversing epithelial-mesenchymal transition. Here, two human epidermal growth factor receptor 2-positive breast cancer cell lines, SKBR3 and BT474, were exposed to increasing concentrations of lapatinib to establish lapatinib-resistant cultures. Lapatinib-resistant SKBR3 and BT474 cells exhibited up-regulation of the phenotypic epithelial-mesenchymal transition markers Snail, vimentin and α-smooth muscle actin, accompanied by activation of nuclear factor-кB and Src and a concomitant increase in stem cell marker expression (CD44(high)/CD24(low)), compared to naive lapatinib-sensitive SKBR3 and BT474 cells, respectively. Interestingly, niclosamide reversed epithelial-mesenchymal transition, induced apoptosis and inhibited cell growth by perturbing aberrant signaling pathway activation in lapatinib-resistant human epidermal growth factor receptor 2-positive cells. The ability of niclosamide to alleviate stem-like phenotype development and invasion was confirmed. Collectively, our results demonstrate that lapatinib resistance correlates with epithelial-mesenchymal transition and that niclosamide inhibits lapatinib-resistant cell viability and epithelial-mesenchymal transition. These findings suggest a role of niclosamide or derivatives optimized for more favorable bioavailability not only in reversing lapatinib resistance but also in reducing metastatic potential during the treatment of human epidermal growth factor receptor 2-positive breast cancer.

Vishnoi M, Peddibhotla S, Yin W, et al.
The isolation and characterization of CTC subsets related to breast cancer dormancy.
Sci Rep. 2015; 5:17533 [PubMed] Article available free on PMC after 24/06/2017 Related Publications
Uncovering CTCs phenotypes offer the promise to dissect their heterogeneity related to metastatic competence. CTC survival rates are highly variable and this can lead to many questions as yet unexplored properties of CTCs responsible for invasion and metastasis vs dormancy. We isolated CTC subsets from peripheral blood of patients diagnosed with or without breast cancer brain metastasis. CTC subsets were selected for EpCAM negativity but positivity for CD44(+)/CD24(-) stem cell signature; along with combinatorial expression of uPAR and int β1, two markers directly implicated in breast cancer dormancy mechanisms. CTC subsets were cultured in vitro generating 3D CTC tumorspheres which were interrogated for biomarker profiling and biological characteristics. We identified proliferative and invasive properties of 3D CTC tumorspheres distinctive upon uPAR/int β1 combinatorial expression. The molecular characterization of uPAR/int β1 CTC subsets may enhance abilities to prospectively identify patients who may be at high risk of developing BCBM.

Madaras L, Balint N, Gyorffy B, et al.
BRCA Mutation-Related and Claudin-Low Breast Cancer: Blood Relatives or Stepsisters.
Pathobiology. 2016; 83(1):1-12 [PubMed] Related Publications
BACKGROUND: BRCA mutation-associated (BRCAmut) breast cancer represents a heterogeneous group displaying certain molecular features. Claudin-low breast cancers (CLBC) overlap with characteristics of BRCAmut tumors; therefore, we have investigated whether these are identical subtypes.
METHODS: Using public gene expression data, CLDN, CDH1, 9-cell line claudin-low predictor (9CLCLP) and PAM50 expression was evaluated in BRCAmut and BRCA wild-type (BRCAwt) breast cancer cases focusing on their possible overlap with the CLBC subtype. A separate formalin-fixed, paraffin-embedded (FFPE) cohort of 22 BRCAmut and 19 BRCAwt tumor tissues was used for immunohistochemical examination of AR, CD24, CD44, CK5/6, claudin-1, -3, -4 and -7, E-cadherin, EGFR, estrogen receptor (ER), EZH2, HER2, Ki67, p53, progesterone receptor (PgR) and vimentin expression.
RESULTS: In the data sets, CLDN1 (ROC = 0.785, p < 0.001), CDH1 (ROC = 0.785, p < 0.001), CLDN7 (ROC = 0.723, p < 0.001), CLDN3 (ROC = 0.696, p = 0.020) and CLDN4 (ROC = 0.685, p = 0.027) were expressed at higher level in BRCAmut than BRCAwt tumor tissue. The PAM50 subtype differed from the assigned immunohistochemistry (IHC)-based subtype in 30%. Based on accessible 9CLCLP predictor genes, BRCAmut breast cancer does not display the claudin-low phenotype. Utilizing FFPE samples, claudins were evidently expressed in both BRCAmut and BRCAwt cases. However, at the protein level, only claudin-3 expression was higher in BRCAmut tumors, while claudin-1, -4 and -7 and E-cadherin expression was lower compared to BRCAwt cases. A CD24low/CD44high phenotype was found in BRCAmut tumors upon comparison with BRCAwt cases (p < 0.001 and p = 0.001, respectively).
CONCLUSIONS: There is a prominent correlation between the genes under focus herein and BRCA mutation status. BRCAmut tumors bear stem cell characteristics displaying a distinct cell adhesion molecule profile characterized by high expression of CDH1 and CLDN4 according to public gene expression data set analysis, and higher claudin-3 expression as detected by IHC; thus, BRCAmut breast carcinomas are not identical with the previously identified claudin-low subtype of breast cancer.

Ge G, Zhou C, Ren Y, et al.
Enhanced SLC34A2 in breast cancer stem cell-like cells induces chemotherapeutic resistance to doxorubicin via SLC34A2-Bmi1-ABCC5 signaling.
Tumour Biol. 2016; 37(4):5049-62 [PubMed] Related Publications
Even though early detection methods and treatment options are greatly improved, chemoresistance is still a tremendous challenge for breast cancer therapy. Breast cancer stem cells (BCSCs) represent a subpopulation that is central to chemoresistance. We aim to investigate the relationship between SLC34A2 and chemoresistance in BCSCs and identify the underlying mechanisms by which SLC34A2 regulates chemoresistance in BCSCs. Fluorescence Activated Cell Sorting (FACS) analysis showed the presence of a variable fraction of CD44(+)CD24(-) cells in 25 out of 25 breast cancer samples. We cultured primary breast cancer sample cells and breast cancer cell line cells to induce sphere formation in serum-free medium. Following sorting of CD44(+)CD24(-) cells from spheres, we showed that CD44(+)CD24(-) cells displayed stem cell-like features and were resistant to chemotherapy drug doxorubicin. Significantly, enhanced SLC34A2 expression correlated with chemoresponse and survival of breast cancer patients. We subsequently indicated that increased SLC34A2 expression in BCSCs directly contributed to their chemoresistance by a series of in vitro and in vivo experiments. Furthermore, we demonstrated that SLC34A2 induced chemoresistance in BCSCs via SLC34A2-Bmi1-ABCC5 signaling. Finally, we showed that ABCC5 was a direct transcriptional target of Bmi1 by chromatin immunoprecipitation (ChIP). In conclusion, our work indicated that decreased SLC34A2 expression sensitized BCSCs to doxorubicin via SLC34A2-Bmi1-ABCC5 signaling and shed new light on understanding the mechanism of chemoresistance in BCSCs. This study not only bridges the missing link between stem cell-related transcription factor (Bmi1) and ABC transporter (ABCC5) but also contributes to development of potential therapeutics against breast cancer.

Murat Dogan S, Pinar Ercetin A, Altun Z, et al.
Gene expression characteristics of breast cancer stem cells.
J BUON. 2015 Sep-Oct; 20(5):1304-13 [PubMed] Related Publications
PURPOSE: Breast cancer stem cells have been found to be responsible for tumorigenic potential and resistance to therapy. This study aimed at comparing gene expression profiles in breast cancer, based on the differences of stem cells in their biological characteristics.
METHODS: Four breast cancer cell lines with different molecular and biological characteristics were used to analyze 84 breast cancer-related gene expressions. These were the ductal human epithelial breast cancer cell line T47D (HTB-133) with metastatic origin, the invasive ductal human breast carcinoma cell line MDA-MB-231 (HTB-26), the ductal human epithelial breast cancer cell line BT-474 (HTB-20) and the human metastatic breast adenocarcinoma cell line MCF-7 (HTB-22).
RESULTS: There were significant differences between the breast cancer cells and the stem cells, particularly in angiogenesis, migration, proliferation and the expression of the DNA repair genes.
CONCLUSION: These data indicated the absence of a general cancer stem cell in breast cancer. Our study supports the use of the term "breast cancer initiating cells" instead of breast cancer stem cells. All of these genetic differences should be taken into account in the planning of final therapeutic approach.

Kastrati I, Litosh VA, Zhao S, et al.
A novel aspirin prodrug inhibits NFκB activity and breast cancer stem cell properties.
BMC Cancer. 2015; 15:845 [PubMed] Article available free on PMC after 24/06/2017 Related Publications
INTRODUCTION: Activation of cyclooxygenase (COX)/prostaglandin and nuclear factor κB (NFκB) pathways can promote breast tumor initiation, growth, and progression to drug resistance and metastasis. Thus, anti-inflammatory drugs have been widely explored as chemopreventive and antineoplastic agents. Aspirin (ASA), in particular, is associated with reduced breast cancer incidence but gastrointestinal toxicity has limited its usefulness. To improve potency and minimize toxicity, ASA ester prodrugs have been developed, in which the carboxylic acid of ASA is masked and ancillary pharmacophores can be incorporated. To date, the effects of ASA and ASA prodrugs have been largely attributed to COX inhibition and reduced prostaglandin production. However, ASA has also been reported to inhibit the NFκB pathway at very high doses. Whether ASA prodrugs can inhibit NFκB signaling remains relatively unexplored.
METHODS: A library of ASA prodrugs was synthesized and screened for inhibition of NFκB activity and cancer stem-like cell (CSC) properties, an important PGE2-and NFκB-dependent phenotype of aggressive breast cancers. Inhibition of NFκB activity was determined by dual luciferase assay, RT-QPCR, p65 DNA binding activity and Western blots. Inhibition of CSC properties was determined by mammosphere growth, CD44(+)CD24(-)immunophenotype and tumorigenicity at limiting dilution.
RESULTS: While we identified multiple ASA prodrugs that are capable of inhibiting the NFκB pathway, several were associated with cytotoxicity. Of particular interest was GTCpFE, an ASA prodrug with fumarate as the ancillary pharmacophore. This prodrug potently inhibits NFκB activity without innate cytotoxicity. In addition, GTCpFE exhibited selective anti-CSC activity by reducing mammosphere growth and the CD44(+)CD24(-)immunophenotype. Moreover, GTCpFE pre-treated cells were less tumorigenic and, when tumors did form, latency was increased and growth rate was reduced. Structure-activity relationships for GTCpFE indicate that fumarate, within the context of an ASA prodrug, is essential for anti-NFκB activity, whereas both the ASA and fumarate moieties contributed to attenuated mammosphere growth.
CONCLUSIONS: These results establish GTCpFE as a prototype for novel ASA-and fumarate-based anti-inflammatory drugs that: (i) are capable of targeting CSCs, and (ii) may be developed as chemopreventive or therapeutic agents in breast cancer.

Liu T, Hu K, Zhao Z, et al.
MicroRNA-1 down-regulates proliferation and migration of breast cancer stem cells by inhibiting the Wnt/β-catenin pathway.
Oncotarget. 2015; 6(39):41638-49 [PubMed] Article available free on PMC after 24/06/2017 Related Publications
We investigated the miRNA profiles of breast cancer stem cells (CSCs) and non-CSC tumor cells by miRNA microarray and determined the effect of altered miR-1 expression on proliferation and migration of breast CSCs. The potential targets of miR-1 in the Wnt/β-catenin signaling were characterized by bioinformatics analysis and luciferase assay. We found that 14 miRNAs were up-regulated and 13 were down-regulated in the ESA+CD44+CD24-lineage- CSCs, related to ESA+CD44-CD24+lineage- non-CSC tumor cells. The miR-1 expression was associated inversely with aggressiveness of breast cancers. Furthermore, enhanced miR-1 expression decreased the percentages of SKBR3/CSCs and miR-1 inhibition increased the percentages of MCF-7/CSCs. Enhanced miR-1 expression significantly reduced the Frizzled 7 and Tankyrase-2 (TNKS2)-regulated luciferase activity in 293T cells and decreased Frizzled 7, TNKS2, c-Myc, octamer-binding transcription factor 4 (Oct4) and Nanog expression and the ratios of nuclear to cytoplasmic β-catenin as well as β-catenin-dependent luciferase activity in breast CSCs in vitro. miR-1 inhibited proliferation, migration and wound healing of breast CSCs in vitro. Enhanced miR-1 expression inhibited the growth of implanted MCF-7/CSCs while miR-1 inhibition promoted the growth of implanted MCF-7/CSCs in vivo. Our data indicate that miR-1 down-regulates breast CSC stemness, proliferation and migration by targeting the Frizzled 7 and TNKS2 to inhibit the Wnt/β-catenin signaling.

Disclaimer: This site is for educational purposes only; it can not be used in diagnosis or treatment.

Cite this page: Cotterill SJ. CD24, Cancer Genetics Web: Accessed:

Creative Commons License
This page in Cancer Genetics Web by Simon Cotterill is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
Note: content of abstracts copyright of respective publishers - seek permission where appropriate.

 [Home]    Page last revised: 16 March, 2017     Cancer Genetics Web, Established 1999