ITK

Gene Summary

Gene:ITK; IL2 inducible T-cell kinase
Aliases: EMT, LYK, LPFS1, PSCTK2
Location:5q33.3
Summary:This gene encodes an intracellular tyrosine kinase expressed in T-cells. The protein contains both SH2 and SH3 domains which are often found in intracellular kinases. It is thought to play a role in T-cell proliferation and differentiation. [provided by RefSeq, Jul 2008]
Databases:VEGA, OMIM, HGNC, Ensembl, GeneCard, Gene
Protein:tyrosine-protein kinase ITK/TSK
Source:NCBIAccessed: 16 March, 2017

Ontology:

What does this gene/protein do?
Show (18)
Pathways:What pathways are this gene/protein implicaed in?
Show (3)

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.

  • Western Blotting
  • Intracellular Signaling Peptides and Proteins
  • Chromosome 5
  • Syk Kinase
  • Herpesvirus 4, Human
  • Cancer Gene Expression Regulation
  • Genetic Predisposition
  • Childhood Cancer
  • Phosphorylation
  • Lymphoma, T-Cell, Peripheral
  • Immunohistochemistry
  • Biomarkers, Tumor
  • Disease Models, Animal
  • Oncogene Fusion Proteins
  • Immunoblastic Lymphadenopathy
  • CD Antigens
  • Immunophenotyping
  • Pyrimidines
  • T-Lymphocyte Gene Rearrangement
  • Cytokines, Interleukin-2
  • Phosphoproteins
  • Trisomy
  • Tyrosine
  • Germ-Line Mutation
  • FISH
  • Antigens, Differentiation, T-Lymphocyte
  • Signal Transduction
  • Protein-Tyrosine Kinases
  • Biopsy
  • Vincristine
  • Phenotype
  • Epstein-Barr Virus Infections
  • Chromosome 9
  • T-Lymphocytes
  • T-Lymphocytes, Helper-Inducer
  • Adolescents
  • T-Cell Antigen Receptors
  • T-Cell Lymphoma
  • Gene Expression Profiling
Tag cloud generated 16 March, 2017 using data from PubMed, MeSH and CancerIndex

Specific Cancers (1)

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

Entity Topic PubMed Papers
-ITK and T-Cell Lymphoma View Publications15

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

Latest Publications: ITK (cancer-related)

Xia S, Ji R, Zhan W
Long noncoding RNA papillary thyroid carcinoma susceptibility candidate 3 (PTCSC3) inhibits proliferation and invasion of glioma cells by suppressing the Wnt/β-catenin signaling pathway.
BMC Neurol. 2017; 17(1):30 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The dysregulation of long noncoding RNAs (lncRNAs) has been identified in a variety of cancers. An increasing number of studies have found the critical role of lncRNAs in the regulation of cellular processes, such as proliferation, invasion and differentiation. Long noncoding RNA papillary thyroid carcinoma susceptibility candidate 3 (PTCSC3) is a novel lncRNA that was primarily detected in papillary thyroid carcinoma. However, the biological function and molecular mechanism of lncRNA PTCSC3 in glioma are still unknown.
METHODS: The expression level of lncRNA PTCSC3 in human microglia and glioma cell lines was examined using quantitative real-time polymerase chain reaction (qRT-PCR). The influence of lncRNA PTCSC3 on cell proliferation were studied using the cell counting kit-8, and cell cycle and apoptosis were analyzed by flow cytometry assays. The migration and invasion abilities were investigated by transwell and wound healing assays. The target genes of lncRNA PTCSC3 were explored by qRT-PCR, immunofluorescence and western blot.
RESULTS: LncRNA PTCSC3 was significantly downregulated in glioma cell lines. The overexpression of lncRNA PTCSC3 suppressed proliferation and induced apoptosis in U87 and U251 cells. Additionally, the overexpression of lncRNA PTCSC3 inhibited the migration and invasion of U87 and U251 cells. Moreover, lncRNA PTCSC3 inhibited the epithelial-mesenchymal transition of U87 cells. The study also demonstrated that LRP6, as a receptor of the Wnt/β-catenin pathway, was a target of lncRNA PTCSC3. By evaluating the expression levels of Axin1, active β-catenin, c-myc, and cyclin D1, the study indicated that lncRNA PTCSC3 inhibited the activation of the Wnt/β-cateninpathway through targeting LRP6.
CONCLUSIONS: LncRNA PTCSC3 inhibits the proliferation and migration of glioma cells and suppresses Wnt/β-catenin signaling pathway by targeting LRP6. LncRNA PTCSC3 is a potential therapeutic target for treatment of glioma.

Ryu SH, Heo SH, Park EY, et al.
Selumetinib Inhibits Melanoma Metastasis to Mouse Liver via Suppression of EMT-targeted Genes.
Anticancer Res. 2017; 37(2):607-614 [PubMed] Related Publications
AIM: We investigated the therapeutic effects of a mitogen-activated protein (MEK) inhibitor, selumetinib, in a hepatic melanoma metastasis model and studied its possible mechanism of action.
MATERIALS AND METHODS: Melanoma cell lines were exposed to selumetinib under different experimental conditions. We established a mouse model of liver metastasis and treated mice orally with vehicle or selumetinib and then evaluated metastasis progress.
RESULTS: Growth inhibition was observed in melanoma cells as a consequence of G1-phase cell-cycle arrest and the subsequent induction of apoptosis in a dose- and time-dependent manner. Mice with established liver metastases that were treated with selumetinib exhibited significantly less tumor progression than vehicle-treated mice. c-Myc expression in metastasized liver tissues were suppressed by selumetinib. Moreover, oral treatment with selumetinib modulated expression of epithelial-to-mesenchymal transition- and metastasis-related genes, including integrin alpha-5 (ITGA5), jagged 1 (JAG1), zinc finger E-box-binding homeobox 1 (ZEB1), NOTCH, and serpin peptidase inhibitor clade E (SERPINE1).
CONCLUSION: We established a mouse model of hepatic metastasis using a human melanoma cell line, such models are essential in elucidating the therapeutic effects of anti-metastatic drugs. Our data suggest the possibility that selumetinib presents a new strategy to treat liver metastasis in patients with melanoma by suppressing epithelial-to-mesenchymal transition-related genes.

Ablin RJ, Owen S, Jiang WG
Prostate Transglutaminase (TGase-4) Induces Epithelial-to-Mesenchymal Transition in Prostate Cancer Cells.
Anticancer Res. 2017; 37(2):481-487 [PubMed] Related Publications
More men die with prostate cancer (PCa) than from it. However, once PCa is no longer organ-confined, it is associated with significant mortality. Epithelial-to-mesenchymal transition (EMT) is one mechanism facilitating progression in cancer. Our studies of transglutaminase-4 (TGase-4), a member of the TGase family, expressed in the prostate gland, have implicated it in the regulation of the invasive properties of PCa. The present study investigated the role of TGase-4 on EMT of PCa cells.
MATERIALS AND METHODS: A panel of PCa cell lines: CA-HPV-10, PZ-HPV-7, PC-3 and DU-145 were used. An anti-TGase-4 transgene was constructed to eliminate the expression of TGase-4 in CA-HPV-10 (positive for TGase-4). An expression construct for human TGase-4 was used to transfect PCa cells negative for TGase-4. The pattern of E-cadherin, N-cadherin and vimentin in these cells were evaluated using immunofluorescent staining. Cell motility was assessed using scratch wounding and ekectric cell-substrate impedance sensing (ECIS) assays.
RESULTS: Treatment of PZ-HPV-7 and CA-HPV-10 cells with rhTGase-4 resulted in a significant increase in cell migration (1,407.9 Ω±6.4 Ω vs. 1,691.2 Ω±8.3 Ω in non-treated and rhTGase-4 treated cells, respectively, p<0.01). Cells strongly expressing E-cadherin showed substantial changes of E-cadherin staining in that, after treatment with TGase-4, the intercellular staining of E-cadherin was diminished. Concomitantly, there was acquisition of N-cadherin in TGase-4-treated cells. Elimination of TGase-4 from CA-HPV-10 cells significantly decreased cell motility (128.1 Ω±107.4 Ω vs. 31.7 Ω±26.2 Ω, in CA-HPV-10 control and CA-HPV-10/TGase-4 knockout cells). Knocking- out TGase-4 from CA-HPV-10 cells also resulted in substantial loss of N-cadherin in the cells.
CONCLUSION: TGase-4 resulted in loss of E-cadherin/acquisition of N-cadherin and cell migration indicating it is a keen regulator of EMT in prostate epithelia-derived cancer cells. In concert with its other properties involved in disease progression, the present observations suggest TGase-4 as a prospective marker of disease progression.

Ma F, Wang SH, Cai Q, et al.
Long non-coding RNA TUG1 promotes cell proliferation and metastasis by negatively regulating miR-300 in gallbladder carcinoma.
Biomed Pharmacother. 2017; 88:863-869 [PubMed] Related Publications
BACKGROUND: As we all know, long non-coding RNAs (lncRNAs) have been reported to play vital roles in various human cancers. In this study, we aimed to explore the role of lncRNA TUG1 in gallbladder carcinoma (GBC) development.
METHODS: Total RNA was extracted from the tissues of thirty GBC patients, four GBC cell lines. We detected the expression levels of TUG1 using quantitative real-time PCR. We performed CCK8, colony formation, transwell invasion and apoptosis assays to study the effects of TUG1 on GBC cell proliferation and invasion. Western blot assay was performed to assess to the expression level of epithelial-mesenchymal transition (EMT) markers in transforming growth factor-β1 (TGF-β1) treated and TUG1 knockdown GBC cell. Lastly, dual-luciferase reporter assay and quantitative real-time PCR were performed to verify the potential target microRNAs (miRNAs) of TUG1.
RESULTS: TUG1 expression was significantly overexpressed in GBC tissues. Functionally, this study demonstrated that knockdown of TUG1 significantly inhibited GBC cell proliferation, metastasis. Mechanically, we found that TUG1 is upregulated by TGF-β1, and knockdown of TUG1 inhibited GBC cell EMT. Furthermore, we identified that miR-300, which has been reported as a suppressor in other types of cancer, is negatively regulated by TUG1.
CONCLUSIONS: LncRNA TUG1 promotes GBC cell proliferation, metastasis and EMT progression by functioning as a miRNA sponge to abrogate the endogenous effect of miR-300.

Yao GL, Pan CF, Xu H, et al.
Long noncoding RNA RP11-766N7.4 functions as a tumor suppressor by regulating epithelial-mesenchymal transition in esophageal squamous cell carcinoma.
Biomed Pharmacother. 2017; 88:778-785 [PubMed] Related Publications
BACKGROUND: Numerous studies have proved that long non-coding RNAs participate in the initiation and metastasis of various cancers including esophageal squamous cell carcinoma (ESCC). Recently, a novel long non-coding RNA RP11-766N7.4 was discovered in a variety of human tissues. However, its role in oncogenesis and tumor metastasis remains unknown.
METHODS: To investigate the function of long noncoding RNA RP11-766N7.4 in ESCC, RT-qPCR was used to monitor the expression level of long non-coding RNA RP11-766N7.4 in ESCC cell lines and 50 paired ESCC tissues. Moreover, the association between long non-coding RNA RP11-766N7.4 expression level and clinicopathological characteristics as well as 5-year survival rate of ESCC patients was evaluated. Furthermore, function assays containing cell proliferation assay, flow cytometry, Colony Formation, wound healing assay and Transwell assays were conducted to investigate the role of long noncoding RNA RP11-766N7.4 in ESCC. Western blotting assay were used to explore the regulation mechanism.
RESULTS: In this study, we found that long noncoding RNA RP11-766N7.4 was downregulated in ESCC tissues and cell lines and correlated with lymph node metastasis, tumor stage and survival rate. Results also revealed that long noncoding RNA RP11-766N7.4 had no significant effect on cell proliferation, cell cycle or cell apoptosis of ESCC cells. In addition, long noncoding RNA RP11-766N7.4 knockdown promoted cellular migration and invasion via inducing EMT process, and overexpression of long noncoding RNA RP11-766N7.4 inhibited cellular migration and invasion by suppressing EMT process.
CONCLUSION: Our study suggested that long noncoding RNA RP11-766N7.4 acts as a tumor suppressor in ESCC carcinogenesis and metastasis, and may be a potential prognostic mark and a therapeutic target for ESCC.

Hao Y, Yang X, Zhang D, et al.
Long noncoding RNA LINC01186, regulated by TGF-β/SMAD3, inhibits migration and invasion through Epithelial-Mesenchymal-Transition in lung cancer.
Gene. 2017; 608:1-12 [PubMed] Related Publications
Accumulating evidence suggests that long noncoding RNAs (lncRNAs) are crucial regulators of the Epithelial-Mesenchymal-Transition (EMT). TGF-β signaling is a major inducer of EMT and can facilitate lung cancer metastasis. However, the role of lncRNAs in this process remains largely unknown. Here, we have identified 291 lncRNAs which were differentially expressed in lung cancer tissues compared with adjacent normal tissues. Of these, the gene body or vicinity of 19 transcripts were also bound by SMAD3. The expression of LINC01186 was significantly decreased in A549 cells treated with TGF-β1. Furthermore, LINC01186 was stably down-regulated in lung cancer tissues compared with normal tissues in TCGA data sets and another published lung cancer data sets. The bioinformatics analysis suggested that LINC01186 was associated with TGF-β and might participate in EMT process. Moreover, knocking-down LINC01186 promoted cell migration and invasion, whereas, LINC01186 overexpression prevented cell metastasis. Importantly, LINC01186 expression was regulated by SMAD3. And LINC01186 affected several EMT markers expression. These findings suggest that LINC01186, a mediator of TGF-β signaling, can play a significant role in the regulation of EMT and lung cancer cell migration and invasion.

Lu J, Xu Y, Wei X, et al.
Emodin Inhibits the Epithelial to Mesenchymal Transition of Epithelial Ovarian Cancer Cells via ILK/GSK-3β/Slug Signaling Pathway.
Biomed Res Int. 2016; 2016:6253280 [PubMed] Free Access to Full Article Related Publications
Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. Despite the anticancer capabilities of emodin observed in many cancers, including EOC, the underlying molecular mechanism remains to be elucidated. A crucial link has been discovered between the acquisition of metastatic traits and the epithelial-mesenchymal transition (EMT). The present study aimed to determine whether emodin could inhibit the EMT of EOC cells and explore the underlying mechanism. The CCK-8 assay and transwell assay showed that emodin effectively repressed the abilities of proliferation, invasion, and migration in A2780 and SK-OV-3 cells. The Western blot showed that emodin upregulated epithelial markers (E-cadherin and Claudin) while it downregulated mesenchymal markers (N-cadherin and Vimentin) and transcription factor (Slug) in a dose-dependent fashion. After transfection of siRNA-Slug, both Slug and N-cadherin were downregulated in EOC cells while E-cadherin was upregulated, which was intensified by emodin. Besides, emodin decreased the expression of ILK, p-GSK-3β, β-catenin, and Slug. Transfection of siRNA-ILK also achieved the same effects, which was further strengthened by following emodin treatment. Nevertheless, SB216763, an inhibitor of GSK-3β, could reverse the effects of emodin except for ILK expression. These findings suggest that emodin inhibited the EMT of EOC cells via ILK/GSK-3β/Slug signaling pathway.

Pan Y, Qin T, Yin S, et al.
Long non-coding RNA UC001kfo promotes hepatocellular carcinoma proliferation and metastasis by targeting α-SMA.
Biomed Pharmacother. 2017; 87:669-677 [PubMed] Related Publications
Several long non-coding RNAs (lncRNAs) have been investigated and found to be correlated with the behaviours and prognosis of hepatocellular carcinoma (HCC); Specifically, we revealed that the lncRNA UC001kfo was differentially expressed in HCC tissues compared with normal liver tissues using lncRNA microarrays, but its functional role in cancers, including HCC, has not yet been elucidated. The present study found that the expression of UC001kfo was upregulated in HCC tissues and cell lines in comparison with tumour-adjacent tissues and normal hepatocytes, respectively. In addition, a high UC001kfo level was determined to be correlated with macro-vascular invasion and TNM stage of HCC. Specifically, patients with high UC001kfo expression displayed a significantly lower overall survival rate and progression-free survival rate. Moreover, both univariate and multivariate COX regression analyses identified TNM stage and high UC001kfo expression as risk factors for poor prognosis in HCC patients. In addition, UC001kfo was verified to promote the proliferation, metastasis and epithelial-mesenchymal transition (EMT) in HCC cells in both in vitro and in vivo assays. Mechanistically, α-SMA was indicated as a potential target gene of UC001kfo in mediating HCC metastasis. In conclusion, UC001kfo promotes HCC proliferation and metastasis by targeting α-SMA, and UC001kfo may potentially serve as a prognostic marker and a therapeutic target for treatment of HCC.

Liang X, Men QL, Li YW, et al.
Silencing of Armadillo Repeat-Containing Protein 8 (ARMc8) Inhibits TGF-β-Induced EMT in Bladder Carcinoma UMUC3 Cells.
Oncol Res. 2017; 25(1):99-105 [PubMed] Related Publications
Armadillo repeat-containing protein 8 (ARMc8) is a key factor in regulating cell migration, proliferation, tissue maintenance, and tumorigenesis. However, its role in bladder cancer remains unknown. Thus, in this study we sought to investigate the effect of ARMc8 on the epithelial-to-mesenchymal transition (EMT) progress in bladder cancer cells induced by transforming growth factor-β1 (TGF-β1). Our results found that ARMc8 was highly expressed in bladder cancer cell lines. ARMc8 silencing inhibited the TGF-β1-induced migration and invasion and suppressed the EMT progress in bladder cancer cells. Furthermore, ARMc8 silencing inhibited the TGF-β1-induced expression of β-catenin, cyclin D1, and c-myc in bladder cancer cells. In conclusion, the present study demonstrates a novel function for ARMc8, which acts as a mediator for TGF-β1-induced cell migration/invasion through modulation of the Wnt/β-catenin signaling pathway in bladder cancer cells. This study suggests that ARMc8 may be a potential therapeutic target for the development of therapies for bladder cancer.

Zhang M, Wang D, Zhu T, Yin R
RASSF4 Overexpression Inhibits the Proliferation, Invasion, EMT, and Wnt Signaling Pathway in Osteosarcoma Cells.
Oncol Res. 2017; 25(1):83-91 [PubMed] Related Publications
RASSF4, a member of the RASSF family, is broadly expressed in normal tissues but often inactivated in human cancers. Despite various studies on RASSF4, its role in osteosarcoma remains unclear. Therefore, in this study, we investigated the effects of RASSF4 expression on osteosarcoma cells and explored the underlying mechanism. The results of our study showed that RASSF4 was lowly expressed in osteosarcoma tissues and cells. RASSF4 overexpression significantly inhibited proliferation, migration, and invasion as well as the EMT process in osteosarcoma cells. Meanwhile, we found that RASSF4 overexpression markedly decreased the protein expression of β-catenin, cyclin D1, and c-Myc in osteosarcoma cells. In conclusion, our findings showed that RASSF4 overexpression inhibits proliferation, invasion, EMT, and Wnt signaling pathway in osteosarcoma cells. Thus, RASSF4 may be considered a novel target for osteosarcoma treatment.

Wang K, Ren Y, Liu Y, et al.
Tumor Necrosis Factor (TNF)-α-Induced Protein 8-like-2 (TIPE2) Inhibits Proliferation and Tumorigenesis in Breast Cancer Cells.
Oncol Res. 2017; 25(1):55-63 [PubMed] Related Publications
Tumor necrosis factor-α (TNF-α)-induced protein 8-like-2 (TNFAIP8L2 or TIPE2), a member of the tumor necrosis TNFAIP8 family, was found to be involved in the development and progression of several tumors. However, to date, the role of TIPE2 in breast cancer is still unclear. Thus, the aim of this study is to explore the role of TIPE2 in breast cancer. Our results indicated that TIPE2 expression was significantly decreased in human breast cancer tissue and cell lines. Overexpression of TIPE2 inhibited the proliferation in vitro and tumor xenograft growth in vivo. TIPE2 also inhibited the migration/invasion of breast cancer cells through preventing the epithelial-to-mesenchymal transition (EMT) phenotype. Mechanically, TIPE2 inhibited the expression of β-catenin, cyclin D1, and c-Myc in breast cancer cells. In conclusion, our findings show that TIPE2 may play an important role in breast cancer cell proliferation, invasion, and tumorigenesis in vivo. Therefore, TIPE2 may be a potential molecular target for the treatment of breast cancer.

Shi Y, Sun X, He X
Overexpression of Aristaless-Like Homeobox-4 Inhibits Proliferation, Invasion, and EMT in Hepatocellular Carcinoma Cells.
Oncol Res. 2017; 25(1):11-18 [PubMed] Related Publications
Aristaless-like homeobox-4 (ALX4), a member of the Aristaless-like homeobox family, has been found to be involved in tumor cell proliferation, migration, and invasion. However, the role of ALX4 in hepatocellular carcinoma (HCC) remains largely unclear. Therefore, in this study we investigated the effects of ALX4 on HCC. The study results indicated that the expression of ALX4 was downregulated in HCC tissues and cell lines. Furthermore, we demonstrated that overexpression of ALX4 inhibited the proliferation, invasion, and epithelial-mesenchymal transition (EMT) in HCC cells. We also found that ALX4 had an inhibitory effect on the sonic hedgehog (Shh) signaling pathway. Taken together, the results suggest that ALX4 may be a promising target for HCC treatment.

Gao K, Ji Z, She K, et al.
Long non-coding RNA ZFAS1 is an unfavourable prognostic factor and promotes glioma cell progression by activation of the Notch signaling pathway.
Biomed Pharmacother. 2017; 87:555-560 [PubMed] Related Publications
Survival of patients with glioma remains poor, which is largely attributed to active carcinogenesis. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) play key roles in tumor initiation and progression. However, the function of lncRNA ZFAS1 in glioma is still unclear. In the current study, we found that ZFAS1 was upregulated in glioma tissues and cell lines. High ZFAS1 expression in glioma tissues was significantly correlated with advanced tumor stage and poor overall survival. Furthermore, in vitro assays demonstrated that ZFAS1 inhibition significantly suppressed glioma cell proliferation, migration and invasion. Importantly, we further confirmed that epithelial-mesenchymal transition (EMT) and the Notch signaling pathway was inactivated in the glioma cells after ZFAS1 knockdown. Thus, our findings indicated that ZFAS1 could exhibit a tumor oncogenic role in glioma progression by regulating EMT and Notch signaling pathway. LncRNA ZFAS1 might serve as a therapeutic target for the treatment of glioma patients.

Wang B, Lv K, Chen W, et al.
miR-375 and miR-205 Regulate the Invasion and Migration of Laryngeal Squamous Cell Carcinoma Synergistically via AKT-Mediated EMT.
Biomed Res Int. 2016; 2016:9652789 [PubMed] Free Access to Full Article Related Publications
Previous studies have found that miR-375 and miR-205 were significantly dysregulated in laryngeal squamous cell carcinoma, which contributed to the invasion and migration of LSCC. However, the mechanisms of miR-375 and miR-205 regulating the invasion and migration of LSCC remain unknown. qRT-PCR was performed in 40 pairs of tissue samples to investigate the expression of miR-375 and miR-205 in LSCC and paracarcinoma tissues. To investigate whether or not miR-375 and miR-205 regulated the invasion and migration of LSCC synergistically via AKT-mediated epithelial-mesenchymal transition, miR-375 mimic and miR-205 inhibitor were transfected into SNU899 cells and miR-375 inhibitor and miR-205 mimic were transfected into SNU899 cells, respectively, with or without AKT inhibitor. Then the expressions of miR-375 and miR-205 were validated by qRT-PCR, cell migration and invasion were determined by wound healing assay and transwell invasive assay, and western blot analysis was performed to detect the expression of related proteins. Our results showed that miR-375 and miR-205 regulated the invasion and migration of LSCC via AKT-mediated EMT synergistically. In conclusion, our findings provided not only new information about the molecular mechanism of miRNAs regulating invasion and migration of LSCC, but also a theoretical principle for potential targeting therapy of laryngeal squamous carcinoma.

Zuo ZK, Gong Y, Chen XH, et al.
TGFβ1-Induced LncRNA UCA1 Upregulation Promotes Gastric Cancer Invasion and Migration.
DNA Cell Biol. 2017; 36(2):159-167 [PubMed] Related Publications
According to recent studies, long noncoding RNA urothelial carcinoma associated 1 (UCA1) is involved in the development and progression of many malignant tumors, including gastric cancer (GC). We validated the detailed role of UCA1 in human GC cell lines and GC tissues so as to determine its exact function and the underlying mechanism of GC invasion and migration. In our research, lncRNA-UCA1 was specifically upregulated in GC tissues and cell lines, and augmented GC cell proliferation, and invasive and migratory capabilities. High UCA1 expression in GC was related with poorer prognosis (poorer invasion depth, lymph node metastasis, advanced TNM [T is for the original (primary) tumor, N for nearby (regional) lymph nodes that are involved, and M for distant metastasis] stage, and shorter overall survival). Epithelial mesenchymal transition (EMT), associated with malignancy of cancers, was reported to be responsible for invasion and migration of cancer cells. Transforming growth factor β1 (TGFβ1)-induced EMT was well evaluated. UCA1 silence reduced the protein levels of EMT-related factors, vimentin and snail, while promoted E-cadherin and zonula occludens-1 protein levels in GC cells; the effect of UCA1 could be partly restored by TGFβ1 treatment. Taken together, UCA1 might regulate the tumor proliferation, invasion, and metastasis under TGFβ1 induction. Taken together, UCA1 might present a potential oncogenic factor by promoting GC cell proliferation, invasion, and migration. UCA1 could serve as a novel biomarker for prognosis and a novel therapeutic target of GC treatment.

Li X, Zhang G, Wang Y, et al.
Loss of periplakin expression is associated with the tumorigenesis of colorectal carcinoma.
Biomed Pharmacother. 2017; 87:366-374 [PubMed] Related Publications
Periplakin (PPL), a member of the plakin protein family, has been reported to be down-expressed in urothelial carcinoma. The role of PPL in human colorectal cancer, however, remains largely unknown. Also little is known about the contribution of PPL to the malignant property of colorectal cancer and the intracellular function of PPL. In this study, we demonstrated that PPL was apparently down-expressed in colon carcinomas compared with normal and para-carcinoma tissues, which was correlated with the tumor size. Enforced expression of PPL in HT29 cells inhibited its proliferation evidenced by decreased expression of phosphorylated ERK and PCNA. Furthermore, PPL overexpression could reduce metastasis and epithelial-mesenchymal transition (EMT) of HT29 cells, with decreased expression of N-cadherin, Snail, Slug and α-SMA while increased expression of E-cadherin. On the contrary, the PPL knockdown could promote the cell proliferation, migratory, invasive and EMT ability of HT29 cells. Moreover, enforced expression of PPL induced G1/G0 cell cycle arrest, with decreased cyclin D1, p-Rb and increased expression of p27(kib), which could be reversed by PPL knockdown. In addition, PPL overexpression inhibited the growth of colon cancer allograft in vivo. Taken together, acted as a tumor suppressor in colon cancer progression, PPL could be a new biomarker or potential therapeutic target in colon cancer.

Sun X, Deng Q, Liang Z, et al.
Cigarette smoke extract induces epithelial-mesenchymal transition of human bladder cancer T24 cells through activation of ERK1/2 pathway.
Biomed Pharmacother. 2017; 86:457-465 [PubMed] Related Publications
Bladder cancer is a common genitourinary malignant disease worldwide. Abundant evidence has shown that cigarette smoke (CS) is a crucial risk factor for bladder cancer. Nevertheless, the mechanism underlying the relationship between cigarette smoking and bladder cancer remains unclear. In the present study, we investigated the effects of cigarette smoke extract (CSE) on mitogen-activated protein kinase (MAPK) pathway activation and EMT alterations in human bladder cancer T24 cells, and the preventive effect of extracellular regulated protein kinases 1 and 2 (ERK1/2) inhibitor U0126 was further examined. Our results illustrated that CSE exposure induced morphological change of human bladder cancer T24 cells, enhanced migratory and invasive capacities, reduced epithelial marker expression and elevated mesenchymal marker expression. Meanwhile, exposure of T24 cells to CSE resulted in activation of ERK1/2 pathway as well as activator protein 1 (AP-1) proteins. Interestingly, treatment with ERK1/2 inhibitor U0126 effectively abrogated CSE-triggered EMT and ERK1/2/AP-1 activation. These findings provide novel insight into the molecular mechanisms of CS-associated bladder cancer and may open up new avenues in the search for potential target of bladder cancer intervention.

Xue Y, Xu W, Zhao W, et al.
miR-381 inhibited breast cancer cells proliferation, epithelial-to-mesenchymal transition and metastasis by targeting CXCR4.
Biomed Pharmacother. 2017; 86:426-433 [PubMed] Related Publications
BACKGROUND: MicroRNAs act as posttranscriptional regulators of gene expression in many biological processes, which played a vital role in regulation cancer cells epithelial-to-mesenchymal transition and metastasis. The deregulation of miR-381 has been identified in breast cancer. However, the role and mechanism of miR-381 in breast cancer have not been completely unexplored.
METHODS: Total RNA was extracted from the tissues of 27 patients with breast cancer and two breast cancer cell lines, respectively. The expression levels of miR-381 were examined by quantitative real-time PCR. The stable overexpress or silence miR-381 expression cells lines and control cells line were constructed by lentivirus infection. Subsequently, cell proliferation, cell migration, invasion assay and western blot assay were performed to detect the biological functions of miR-381 in vitro. Moreover, a luciferase reporter assay was conducted to confirm target associations.
RESULTS: In this study, we validated the lower expression of miR-381 in breast cancer tissues than their adjacent non-neoplastic tissues in 27 breast cancer patients. The result also showed that miR-381 was lowly expressed in breast cancer cell lines MCF-7 and MDA-MB-231 than human epithelial cell line MCF-10A. The miR-381 expression was significantly up-regulated under exogenous miRNA-381 treatment in MCF-7 and MDA-MB-231 cells analyzed by quantitative real-time PCR. The results also indicated that an inverse correlation existed between miR-381 expression level and breast cancer cell proliferation, epithelial-to-mesenchymal transition and metastasis. Furthermore, miR-381 was predicted as a regulatory miRNA of CXCR4 in breast cancer, and the data analysis revealed that there was a negatively relationship between miR-381 and CXCR4 expression in breast cancer tissues from the patients. miR-381 played an important role in breast cancer cells proliferation, epithelial-to-mesenchymal transition and metastasis by targeting CXCR4.
CONCLUSIONS: This present study revealed that miR-381 might be considered as a novel therapeutic target for breast cancer treatment.

Rodriguez-Salas N, Dominguez G, Barderas R, et al.
Clinical relevance of colorectal cancer molecular subtypes.
Crit Rev Oncol Hematol. 2017; 109:9-19 [PubMed] Related Publications
Colorectal cancer (CRC) is characterized by alteration of critical pathways such TP53 inactivation, BRAF, PI3CA mutations, APC inactivation, KRAS, TGF-β, CTNNB mutations, disregulation of Epithelial to mesnechymal transition (EMT) genes, WNT signaling activation, MYC amplification, and others. Differences in these molecular events results in differences in phenotypic characteristics of CRC, that have been studied and classified by different models of molecular subtypes. It could have potential applications to prognosis, but also to therapeutical approaches of the CRC patients. We review and summarized the different molecular classifications and try to clarify their clinical and therapeutical relevance.

Zhang M, Sui C, Dai B, et al.
PEG10 is imperative for TGF-β1-induced epithelial‑mesenchymal transition in hepatocellular carcinoma.
Oncol Rep. 2017; 37(1):510-518 [PubMed] Related Publications
Substantial evidence indicates that transforming growth factor-beta 1 (TGF-β1) plays a vital role in epithelial-mesenchymal transition (EMT). PEG10 has been shown involved in invasion and metastasis of tumors. The present study investigated the role of PEG10 in TGF-β1-triggered EMT in hepatocellular carcinoma (HCC) progression. Immunohistochemistry and real-time PCR were used to measure the expression level of PEG10 in clinical HCC tissues with or without lymph node metastasis, and normal tissues. The results showed that PEG10 expression is higher in HCC tissues and associated with overall survival (OS) and lymph node metastasis. Moreover, PEG10 expression level was remarkably higher in hepatic cancer cells than the normal hepatic cell line L02. In the present study, we constructed an adenovirus vector containing the coding area of PEG10 (Ad-PEG10) and infected HepG2 cells and found that overexpression of PEG10 promoted the cell migration, invasion ability and EMT of HepG2 cells. TGF-β1 acted on HepG2 cells by enhancing cell migration, invasion, EMT and upregulating PEG10 expression level. However, cells pretreated with adenovirus vector of PEG10 shRNAs (Ad-shRNA1 and Ad-shRNA2) did not occur EMT prior to TGF-β1 stimulation. Moreover, TGF-β1 did not increase the migration and invasion of cells with PEG10 knockdown and overexpression of PEG10 confers chemoresistance to HepG2 cells. Accordingly, sufficient PEG10 expression level is essential for TGF-β1 induced EMT and associated with the chemoresistance in HepG2 cells.

Sun LL, Song Z, Li WZ, Tang SY
Hypoxia facilitates epithelial-mesenchymal transition-mediated rectal cancer progress.
Genet Mol Res. 2016; 15(4) [PubMed] Related Publications
Rectal cancer is a commonly observed tumor in clinics, and epithelial-mesenchymal transition (EMT) is very important for tumor invasion and metastasis. We established a rectal cancer HCT-116 cell hypoxia model and detected cell proliferation, invasion, and EMT-related protein expression in this model, aiming to analyze the effect of hypoxia on rectal cancer cell EMT. Rectal cancer cell line HCT-116 was cultured in normoxic, hypoxic, or anaerobic environment, and hypoxia-inducible factor-1α (HIF-1α) mRNA expression was detected in the cells by real-time PCR. Cell proliferation was tested by MTT assay; cell invasion was determined by transwell assay, and HIF-1α, epithelial-cadherin, and Snail protein levels were evaluated by western blot analysis. HIF-1α mRNA level significantly increased in the anaerobic group compared to that in the normoxic and hypoxic groups (P < 0.05). HCT-116 cell proliferation in the anaerobic group was obviously higher than that in the other two groups, with the hypoxic group showing stronger proliferative ability than the normoxic group (P < 0.05). Compared to the normoxic group, the HCT-116 cells demonstrated enhanced cell invasion and migration in hypoxic and anaerobic groups. HIF-1α and Snail expressions were upregulated, whereas epithelial-cadherin expression had declined in the hypoxic and anaerobic groups, compared to those in the normal control (P < 0.05). Therefore, hypoxia promoted rectal cancer cell progress by increasing HIF-1α to induce EMT.

Zhou M, Zhang XY, Yu X
Overexpression of the long non-coding RNA SPRY4-IT1 promotes tumor cell proliferation and invasion by activating EZH2 in hepatocellular carcinoma.
Biomed Pharmacother. 2017; 85:348-354 [PubMed] Related Publications
BACKGROUND: Increasing evidences have demonstrated that the dysregulation of long non-coding RNAs (lncRNAs) may act as an important role in tumor progression. The long non-coding RNA SPRY4 intronic transcript 1 (SPRY4-IT1) has been reported in some cancer including regulating cell growth, differentiation, apoptosis, and cancer progression. However, the expression and function of SPRY4-IT1 in the progression of hepatocellular carcinoma (HCC) remain largely unknown.
METHODS: The lncRNA SPRY4-IT1 was detected by quantitative real time PCR (qRT-PCR) in HCC cell lines, CCK8 cell proliferation and transwell invasion assays were performed to detect the GC cell proliferation and invasion abilities. The protein expression of E-cadherin, Vimentin and Twist1 was analyzed by Western blotting assays. Furthermore, RNA immunoprecipitation (RIP) and Chromatin immunoprecipitation (ChIP) assays were used to analyze potential molecular mechanism of SPRY4-IT1 in HCC cells.
RESULTS: We found that SPRY4-IT1 was up-regulated in HCC cell lines. Further function analysis demonstrated that knockdown of SPRY4-IT1 significantly inhibited HCC cells proliferation and invasion, but over-expression of SPRY4-IT1 had the opposite effects on HCC cells in vitro. Moreover, our results also indicated that SPRY4-IT1 over-expression significantly promoted the epithelial-mesenchymal transition (EMT) by up-regulating the transcription factor Twist1 and EMT marker Vimentin and inhibited the E-cadherin expression in MHCC97L cell. Whereas, knockdown of SPRY4-IT1 suppressed the transcription factor Twist1 and EMT marker Vimentin and increased the E-cadherin expression in MHCC97H cells. Mechanisms investigations showed that SPRY4-IT1 interacted with the EZH2 and epigenetically repressed the E-cadherin expression. In vivo, we also demonstrated that the tumor growth was inhibited in SPRY4-IT1 knockdown group compared with the control group.
CONCLUSIONS: These results suggested that lncRNA SPRY4-IT1 might be considered as a therapeutic target in HCC.

Liu B, Pan CF, He ZC, et al.
Long Noncoding RNA-LET Suppresses Tumor Growth and EMT in Lung Adenocarcinoma.
Biomed Res Int. 2016; 2016:4693471 [PubMed] Free Access to Full Article Related Publications
Recently, many studies showed that long noncoding RNAs (lncRNAs) are involved in tumor progression. It is reported that lncRNA-LET is downregulated and has antitumor effect on several types of cancer. This study focuses on the role of lncRNA-LET on lung adenocarcinoma (LAC) progression. RT-PCR results indicated that frequent downregulation of lncRNA-LET in LAC tissues was related to clinicopathologic factors. lncRNA-LET knockdown significantly promoted LAC cell proliferation, invasion, and migration while lncRNA-LET overexpression obviously inhibited LAC cell proliferation, invasion, and migration, indicating a tumor inhibition of lncRNA-LET in LAC progression. Besides, lncRNA-LET inhibited EMT and negatively regulated Wnt/β-catenin pathway in part. Our study suggests that lncRNA-LET exhibits an important tumor-suppressive effect on LAC progression by inhibiting EMT and Wnt/β-catenin pathway, which provides potential therapeutic targets for LAC.

Wang ZH, Li Z, Hu M, et al.
Ovol2 gene inhibits the Epithelial-to-Mesenchymal Transition in lung adenocarcinoma by transcriptionally repressing Twist1.
Gene. 2017; 600:1-8 [PubMed] Related Publications
BACKGROUND: Associated with recent achievements in therapy for advanced lung adenocarcinoma, there will still be an unmet medical need for effective treatment of stage IIIb/IV, and the prognosis of lung cancer is not optimistic till now.
OBJECTIVE: In order to obtain some essential evidences for a potential targeted therapy in lung adenocarcinoma, the effects of Ovol2 gene on Epithelial-to-Mesenchymal Transition (EMT) was observed and the probable mechanisms were analyzed.
METHODS: Ovol2 expression was previously evaluated by immunochemistry in lung adenocarcinoma tissue, and Ovol2 was overexpressed by lentivirus infection in A549 cells. Subsequently, the migration and invasion ability of A549 cells was tested by Transwell and Wound healing experiments. The mRNA level of genes correlated to EMT was detected by Real-time PCR, and the expression of reasonable makers was probed by Western Blot. Finally, rescue experiment, Luciferase assay, and chromatin immunoprecipitation assay were performed to explore the probable mechanisms.
RESULTS: After treated with Ovol2 overexpression, the expression level of E-cadherin was increased, while the expression level of Vimentin and Twist1 was declined not only in the mRNA level but also in the protein level. Moreover, we found that Ovol2 represses transcription of Twist1 by binding to its promoter directly. Wound healing and Transwell assays indicate that the migration and invasion ability were downregulated by Ovol2 in A549 cells.
CONCLUSION: Ovol2 can suppress migration and invasion ability of A549 cells, and prevent EMT by inhibition of Twist1 transcription directly.

Otsuka Y, Sato H, Oikawa T, et al.
High expression of EPB41L5, an integral component of the Arf6-driven mesenchymal program, correlates with poor prognosis of squamous cell carcinoma of the tongue.
Cell Commun Signal. 2016; 14(1):28 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Squamous cell carcinoma of the tongue (tongue SCC) is a major subtype of head and neck squamous cell carcinoma (HNSCC), which is an intractable cancer under current therapeutics. ARF6 and its effector AMAP1 are often overexpressed in different types of cancers, such as breast cancer and renal cancer, and in these cancers, AMAP1 binds to EPB41L5 to promote invasion, metastasis, and drug resistance. EPB41L5 is a mesenchymal-specific protein, normally induced during epithelial-mesenchymal transition (EMT) to promote focal adhesion dynamics. Similarly to breast cancer and renal cancer, the acquisition of mesenchymal phenotypes is the key process that drives the malignancy of HNSCC. We previously showed that the overexpression of AMAP1 in tongue SCC is statistically correlated with the poor outcome of patients. In this study, we examined whether tongue SCC also expresses EPB41L5 at high levels.
RESULTS: Immunohistochemical staining of clinical specimens of tongue SCC demonstrated that high expression levels of EPB41L5 statistically correlate with poor disease-free survival and poor overall survival rates of patients. The tongue SCC cell line SCC-9, which overexpress Arf6 and AMAP1, also expressed EPB41L5 at high levels to promote invasiveness, whereas the weakly invasive SCC-25 cells did not express EPB41L5 at notable levels. Among the different EMT-associated transcriptional factors, ZEB1 was previously found to be most crucial in inducing EPB41L5 in breast cancer and renal cancer. In contrast, expression levels of ZEB1 did not correlate with the expression levels of EPB41L5 in tongue SCC, whereas KLF8 and FOXO3 levels showed positive correlations with EPB41L5 levels. Moreover, silencing of EPB41L5 only marginally improved the drug resistance of SCC-9 cells, even when coupled with ionizing radiation.
CONCLUSION: Our results indicate that activation of the cancer mesenchymal program in tongue SCC, which leads to EPB41L5 expression, closely correlates with the poor prognosis of patients. However, ZEB1 was not the major inducer of EPB41L5 in tongue SCC, unlike in breast cancer and renal cancer. Thus, processes that trigger the mesenchymal program of tongue SCC, which drives their malignancies, seem to be substantially different from those of other cancers.

Choi HS, Cho SG, Kim MK, et al.
SH003 enhances paclitaxel chemosensitivity in MCF-7/PAX breast cancer cells through inhibition of MDR1 activity.
Mol Cell Biochem. 2017; 426(1-2):1-8 [PubMed] Related Publications
Paclitaxel is an anti-cancer drug for treating cancer, but paclitaxel resistance is reported in cancer cells. Multidrug resistance (MDR) is related with the epithelial-to-mesenchymal transition (EMT) mechanism, which plays a key role in cancer metastasis. Moreover, EMT mechanism is connected to tamoxifen resistance in breast cancer cells. Consequently, oncologists are interested in finding new MDR1 inhibitors originating from herbal medicines to have less side-effect. Here, we investigated an inhibition effect of SH003 on MDR1 activity in paclitaxel-resistant MCF-7/PAX breast cancer cells. Our results showed that paclitaxel did not inhibit a proliferation in paclitaxel-resistant MCF-7 breast cancer cells. Paclitaxel-resistant MCF-7 cells showed an increase of MDR1 activity, which was confirmed by measuring an amount of accumulated rhodamine 123 in the cells. Also, qRT-PCR and Western blot assays confirmed that paclitaxel-resistant MCF-7 cells exhibited high MDR1 expression level. Furthermore, paclitaxel-resistant MCF-7 cells showed mesenchymal morphology with alterations of EMT markers, and acquired tamoxifen resistance with a decrease of ERα expression. We also found that a combinatorial treatment of SH003 and paclitaxel in paclitaxel-resistant MCF-7 cells caused apoptosis in synergistic manner, which was due to SH003 inhibition of MDR1 expression. Therefore, SH003 could be a potential agent for overcoming MDR in drug-resistant cancer cells.

Gao K, Yin J, Dong J
Deregulated WWOX is involved in a negative feedback loop with microRNA-214-3p in osteosarcoma.
Int J Mol Med. 2016; 38(6):1850-1856 [PubMed] Related Publications
WW domain-containing oxidoreductase (WWOX) is frequently inactivated in human osteosarcoma, and the restoration of its expression can suppress tumorigenicity in WWOX-negative OS cells. However, its regulatory mechanisms remain to be fully elucidated. In the present study, we demonstrate that WWOX is downregulated and that it regulates proliferation and epithelial-to-mesenchymal transition (EMT)-associated protein expression in osteosarcoma. As shown by our results, WWOX overexpression by transfection with WWOX overexpression plasmids suppressed the proliferation, migration and invasion of osteosarcoma MG63 cells (as shown by MTT and migration and invasion assays). The silencing of microRNA (miR)‑214‑3p by transfection with anti-miR‑14‑3p upregulated WWOX protein expression and also inhibited the proliferation, migration and invasion of osteosarcoma cells. Additionally, we found that WWOX negatively regulated miR‑214‑3p and miR‑10b expression. Our findings define a negative feedback pathway in control of WWOX and miR‑214‑3p expression, thus providing novel molecular targets for the treatment of osteosarcoma.

Senfter D, Madlener S, Krupitza G, Mader RM
The microRNA-200 family: still much to discover.
Biomol Concepts. 2016; 7(5-6):311-319 [PubMed] Related Publications
In the last decade, microRNAs (miRs or miRNAs) became of great interest in cancer research due to their multifunctional and active regulation in a variety of vital cellular processes. In this review, we discuss the miR-200 family, which is composed of five members (miR-141, miR-200a/200b/200c and miR-429). Although being among the best investigated miRNAs in the field, there are still many open issues. Here, we describe the potential role of miR-200 as prognostic and/or predictive biomarker, its influence on motility and cell migration as well as its role in epithelial to mesenchymal transition (EMT) and metastasis formation in different tumour types. Recent studies also demonstrated the influence of miR-200 on drug resistance and described a correlation between miR-200 expression levels and overall survival of patients. Despite intense research in this field, the full role of the miR-200 family in cancer progression and metastasis is not completely understood and seems to differ between different tumour types and different cellular backgrounds. To elucidate these differences further, a finer characterisation of the role of the individual miRNA-200 family members is currently under investigation.

Park GB, Kim D
TLR4-mediated galectin-1 production triggers epithelial-mesenchymal transition in colon cancer cells through ADAM10- and ADAM17-associated lactate production.
Mol Cell Biochem. 2017; 425(1-2):191-202 [PubMed] Related Publications
Toll-like receptor 4 (TLR4) activation is a key contributor to the carcinogenesis of colon cancer. Overexpression of galectin-1 (Gal-1) also correlates with increased invasive activity of colorectal cancer. Lactate production is a critical predictive factor of risk of metastasis, but the functional relationship between intracellular lactate and Gal-1 expression in TLR4-activated colon cancer remains unknown. In this study, we investigated the underlying mechanism and role of Gal-1 in metastasis and invasion of colorectal cancer (CRC) cells after TLR4 stimulation. Exposure to the TLR4 ligand lipopolysaccharide (LPS) increased expression of Gal-1, induced EMT-related cytokines, triggered the activation of glycolysis-related enzymes, and promoted lactate production. Gene silencing of TLR4 and Gal-1 in CRC cells inhibited lactate-mediated epithelial-mesenchymal transition (EMT) after TLR4 stimulation. Gal-1-mediated activation of a disintegrin and metalloproteinase 10 (ADAM10) and ADAM 17 increased the invasion activity and expression of mesenchymal characteristics in LPS-activated CRC cells. Conversely, inhibition of ADAM10 or ADAM17 effectively blocked the generation of lactate and the migration capacity of LPS-treated CRC cells. Thus, the TLR4/Gal-1 signaling pathway regulates lactate-mediated EMT processes through the activation of ADAM10 and ADAM17 in CRC cells.

Wu K, Shen B, Jiang F, et al.
TRPP2 Enhances Metastasis by Regulating Epithelial-Mesenchymal Transition in Laryngeal Squamous Cell Carcinoma.
Cell Physiol Biochem. 2016; 39(6):2203-2215 [PubMed] Related Publications
BACKGROUND/AIM: Surgery and chemotherapy treatments of human laryngeal squamous cell carcinoma (HLSCC) may fail due to metastasis, in which epithelial-mesenchymal transition (EMT) plays an important role. TRPP2, a nonselective cation channel, is expressed in various cell types and participates in many biological processes. Here, we show that TRPP2 enhanced metastasis by regulating EMT.
METHODS: We used immunohistochemistry, western blotting, Ca2+ imaging, transwell and wound healing assays to investigate TRPP2 expression levels in HLSCC tissue, and the role of TRPP2 in invasion and metastasis of a human laryngocarcinoma cell line (Hep2 cell).
RESULTS: We found that TRPP2 protein expression levels were significantly increased in HLSCC tissue; higher TRPP2 levels were associated with decreased patient survival time and degree of differentiation and advanced clinical stage. Knockdown of TRPP2 by transfection with TRPP2 siRNA markedly suppressed ATP-induced Ca2+ release, wound healing, and cell invasion in Hep2 cells. Moreover, TRPP2 siRNA significantly decreased vimentin expression but increased E-cadherin expression in Hep2 cells. In the EMT signalling pathway, TRPP2 siRNA significantly decreased Smad4, STAT3, SNAIL, SLUG and TWIST expression in Hep2 cells.
CONCLUSION: We revealed a previously unknown function of TRPP2 in cancer development and a TRPP2-dependent mechanism underlying laryngocarcinoma cell invasion and metastasis. Our results suggest that TRPP2 may be used as a biomarker for evaluating patient prognosis and as a novel therapeutic target in HLSCC.

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