ADAM10

Gene Summary

Gene:ADAM10; ADAM metallopeptidase domain 10
Aliases: RAK, kuz, AD10, AD18, MADM, CD156c, CDw156, HsT18717
Location:15q21.3
Summary:Members of the ADAM family are cell surface proteins with a unique structure possessing both potential adhesion and protease domains. This gene encodes and ADAM family member that cleaves many proteins including TNF-alpha and E-cadherin. Alternate splicing results in multiple transcript variants encoding different proteins that may undergo similar processing. [provided by RefSeq, Feb 2016]
Databases:VEGA, OMIM, HGNC, Ensembl, GeneCard, Gene
Protein:disintegrin and metalloproteinase domain-containing protein 10
Source:NCBIAccessed: 11 March, 2017

Ontology:

What does this gene/protein do?
Show (37)
Pathways:What pathways are this gene/protein implicaed in?
Show (2)

Cancer Overview

Research Indicators

Publications Per Year (1992-2017)
Graph generated 11 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 11 March, 2017 using data from PubMed, MeSH and CancerIndex

Specific Cancers (3)

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: ADAM10 (cancer-related)

Janiak M, Paskal W, Rak B, et al.
TIMP4 expression is regulated by miR-200b-3p in prostate cancer cells.
APMIS. 2017; 125(2):101-105 [PubMed] Related Publications
In prostate cancer TIMP4 expression level fluctuates with tumor progression. The mechanism and factors influencing its expression remain unclear. The aim of the study was to test the hypothesis on regulation of TIMP4 by microRNA-200b-3p. The levels of TIMP4 and miR-200b-3p expression were determined by real time PCR in 27 prostate carcinomas and eight benign prostatic hyperplasia samples. We found that miR-200b-3p positively correlated with TIMP4 expression in cancer samples (r = 0.46; p < 0.02). Moreover, mean miR-200b-3p level and TIMP4 expression were both higher in cancer tissues compared to benign prostatic hyperplasia samples (p > 0.05). Next, to test probable mechanisms of the regulation androgen-sensitive human prostate adenocarcinoma cells (LNCaP) were transfected with synthetic-miR-200b-3p or its synthetic antagonist. Modulation of miR-200b-3p in LNCaP cells had an impact on TIMP4 expression confirming the observation made in analyzed clinical samples. Two targets of miR-200b-3p: ZEB1 and ETS1 were investigated subsequently as potential regulators of TIMP4, however, no effect of their modulation on TIMP4 expression in LNCaP cells was found. Concluding, miR-200b-3p mediates regulation of TIMP4 expression in prostate cancer but exact mechanism needs to be investigated.

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.

Micocci KC, Moritz MN, Lino RL, et al.
ADAM9 silencing inhibits breast tumor cells transmigration through blood and lymphatic endothelial cells.
Biochimie. 2016 Sep-Oct; 128-129:174-82 [PubMed] Related Publications
ADAMs are transmembrane multifunctional proteins that contain disintegrin and metalloprotease domains. ADAMs act in a diverse set of biological processes, including fertilization, inflammatory responses, myogenesis, cell migration, cell proliferation and ectodomain cleavage of membrane proteins. These proteins also have additional functions in pathological processes as cancer and metastasis development. ADAM9 is a member of ADAM protein family that is overexpressed in several types of human carcinomas. The aim of this study was to investigate the role of ADAM9 in hematogenous and lymphatic tumor cell dissemination assisting the development of new therapeutic tools. The role of ADAM9 in the interaction of breast tumor cells (MDA-MB-231) and endothelial cells was studied through RNA silencing. ADAM9 silencing in MDA-MB-231 cells had no influence in expression of several genes related to the metastatic process such as ADAM10, ADAM12, ADAM17, cMYC, MMP9, VEGF-A, VEGF-C, osteopontin and collagen XVII. However, there was a minor decrease in ADAM15 expression but an increase in that of MMP2. Moreover, ADAM9 silencing had no effect in the adhesion of MDA-MB-231 cells to vascular (HMEC-1 and HUVEC) and lymphatic cells (HMVEC-dLyNeo) under flow condition. Nevertheless, siADAM9 in MDA-MB-231 decreased transendothelial cell migration in vitro through HUVEC, HMEC-1 and HMVEC-dLyNeo (50%, 40% and 32% respectively). These results suggest a role for ADAM9 on the extravasation step of the metastatic cascade through both blood and lymph vessels.

D'Asti E, Rak J
Biological basis of personalized anticoagulation in cancer: oncogene and oncomir networks as putative regulators of coagulopathy.
Thromb Res. 2016; 140 Suppl 1:S37-43 [PubMed] Related Publications
Activation of stromal response pathways in cancer is increasingly viewed as both a local and systemic extension of molecular alterations driving malignant transformation. Rather than reflecting passive and unspecific responses to anatomical abnormalities, the coagulation system is a target of oncogenic deregulation, impacting the role of clotting and fibrinolytic proteins, and integrating hemostasis, inflammation, angiogenesis and cellular growth effects in cancer. These processes signify, but do not depend on, the clinically manifest coagulopathy and thrombosis. In this regard, the role of driver mutations affecting oncoprotein coding genes such as RAS, EGFR or MET and tumour suppressors (PTEN, TP53) are well described as regulators of tissue factor (TF), protease activated receptors (PAR-1/2) and ectopic coagulation factors (FVII). Indeed, in both adult and pediatric brain tumours the expression patterns of coagulation and angiogenesis regulators (coagulome and angiome, respectively) reflect the molecular subtypes of the underlying diseases (glioblastoma or medulloblastoma) as defined by their oncogenic classifiers and clinical course. This emerging understanding is still poorly established in relation to the transforming effects of non-coding genes, including those responsible for the expression of microRNA (miR). Indeed, several miRs have been recently found to regulate TF and other effectors. We recently documented that in the context of the aggressive embryonal tumour with multilayered rosettes (ETMR) the oncogenic driver miR (miR-520g) suppresses the expression of TF and correlates with hypocoagulant tumour characteristics. Unlike in adult cancers, the growth of pediatric embryonal brain tumour cells as spheres (to maintain stem cell properties) results in upregulation of miR-520g and downregulation of TF expression and activity. We postulate that oncogenic protein and miR coding genes form alternative pathways of coagulation system regulation in different tumour settings, a property necessitating more personalised and biologically-based approaches to anticoagulation.

Goel RK, Lukong KE
Understanding the cellular roles of Fyn-related kinase (FRK): implications in cancer biology.
Cancer Metastasis Rev. 2016; 35(2):179-99 [PubMed] Related Publications
The non-receptor tyrosine kinase Fyn-related kinase (FRK) is a member of the BRK family kinases (BFKs) and is distantly related to the Src family kinases (SFKs). FRK was first discovered in 1993, and studies pursued thereafter attributed a potential tumour-suppressive function to the enzyme. In recent years, however, further functional characterization of the tyrosine kinase in diverse cancer types suggests that FRK may potentially play an oncogenic role as well. Specifically, while ectopic expression of FRK suppresses cell proliferation and migration in breast and brain cancers, knockdown or catalytic inhibition of FRK suppresses these cellular processes in pancreatic and liver cancer. Such functional paradox is therefore evidently exhibited in a tissue-specific context. This review sheds light on the recent developments emerged from investigations on FRK which include: (a) a review of the expression pattern of the protein in mammalian cells/tissues, (b) underlying genomic perturbations and (c) a mechanistic function of the enzyme across different cellular environments. Given its functional heterogeneity observed across different cancers, we also discuss the therapeutic significance of FRK.

D'Asti E, Chennakrishnaiah S, Lee TH, Rak J
Extracellular Vesicles in Brain Tumor Progression.
Cell Mol Neurobiol. 2016; 36(3):383-407 [PubMed] Related Publications
Brain tumors can be viewed as multicellular 'ecosystems' with increasingly recognized cellular complexity and systemic impact. While the emerging diversity of malignant disease entities affecting brain tissues is often described in reference to their signature alterations within the cellular genome and epigenome, arguably these cell-intrinsic changes can be regarded as hardwired adaptations to a variety of cell-extrinsic microenvironmental circumstances. Conversely, oncogenic events influence the microenvironment through their impact on the cellular secretome, including emission of membranous structures known as extracellular vesicles (EVs). EVs serve as unique carriers of bioactive lipids, secretable and non-secretable proteins, mRNA, non-coding RNA, and DNA and constitute pathway(s) of extracellular exit of molecules into the intercellular space, biofluids, and blood. EVs are also highly heterogeneous as reflected in their nomenclature (exosomes, microvesicles, microparticles) attempting to capture their diverse origin, as well as structural, molecular, and functional properties. While EVs may act as a mechanism of molecular expulsion, their non-random uptake by heterologous cellular recipients defines their unique roles in the intercellular communication, horizontal molecular transfer, and biological activity. In the central nervous system, EVs have been implicated as mediators of homeostasis and repair, while in cancer they may act as regulators of cell growth, clonogenicity, angiogenesis, thrombosis, and reciprocal tumor-stromal interactions. EVs produced by specific brain tumor cell types may contain the corresponding oncogenic drivers, such as epidermal growth factor receptor variant III (EGFRvIII) in glioblastoma (and hence are often referred to as 'oncosomes'). Through this mechanism, mutant oncoproteins and nucleic acids may be transferred horizontally between cellular populations altering their individual and collective phenotypes. Oncogenic pathways also impact the emission rates, types, cargo, and biogenesis of EVs, as reflected by preliminary analyses pointing to differences in profiles of EV-regulating genes (vesiculome) between molecular subtypes of glioblastoma, and in other brain tumors. Molecular regulators of vesiculation can also act as oncogenes. These intimate connections suggest the context-specific roles of different EV subsets in the progression of specific brain tumors. Advanced efforts are underway to capture these events through the use of EVs circulating in biofluids as biomarker reservoirs and to guide diagnostic and therapeutic decisions.

Ma B, Zhang HY, Bai X, et al.
ADAM10 mediates the cell invasion and metastasis of human esophageal squamous cell carcinoma via regulation of E-cadherin activity.
Oncol Rep. 2016; 35(5):2785-94 [PubMed] Related Publications
A disintegrin and metalloprotease 10 (ADAM10) is involved in the tumorigenesis, invasion and metastasis of several types of solid tumors. However, the potential role of ADAM10 in human esophageal squamous cell carcinoma (ESCC) is not yet well understood. The present study showed that ADAM10 was overexpressed in human ESCC tissues in vivo, and positively associated with depth of tumor invasion, lymph node metastasis and TNM stage, contributing to tumor carcinogenesis, invasion and metastasis. Additionally, ADAM10 was overexpressed in 3 types of ESCC cell lines in vitro, as compared to that in normal esophageal epithelial cells (NEECs); and moreover, ESCC cells with high ADAM10 expression obtained enhanced invasion and migration ability. Subsequently, ADAM10 silencing by small interfering (si) RNA in ESCC cell line, EC-1, reduced cell invasion, migration and proliferation in vitro. Finally, ADAM10 negatively regulated E-cadherin in ESCC in vivo and in vitro. In conclusion, active ADAM10 promotes the carcinogenesis, invasion, metastasis and proliferation of ESCC and controls invasion and metastasis at least in part through the shedding of E-cadherin activity, which makes it a potential biomarker and a useful therapeutic target for ESCC.

Miller MA, Oudin MJ, Sullivan RJ, et al.
Reduced Proteolytic Shedding of Receptor Tyrosine Kinases Is a Post-Translational Mechanism of Kinase Inhibitor Resistance.
Cancer Discov. 2016; 6(4):382-99 [PubMed] Free Access to Full Article Related Publications
UNLABELLED: Kinase inhibitor resistance often involves upregulation of poorly understood "bypass" signaling pathways. Here, we show that extracellular proteomic adaptation is one path to bypass signaling and drug resistance. Proteolytic shedding of surface receptors, which can provide negative feedback on signaling activity, is blocked by kinase inhibitor treatment and enhances bypass signaling. In particular, MEK inhibition broadly decreases shedding of multiple receptor tyrosine kinases (RTK), including HER4, MET, and most prominently AXL, an ADAM10 and ADAM17 substrate, thus increasing surface RTK levels and mitogenic signaling. Progression-free survival of patients with melanoma treated with clinical BRAF/MEK inhibitors inversely correlates with RTK shedding reduction following treatment, as measured noninvasively in blood plasma. Disrupting protease inhibition by neutralizing TIMP1 improves MAPK inhibitor efficacy, and combined MAPK/AXL inhibition synergistically reduces tumor growth and metastasis in xenograft models. Altogether, extracellular proteomic rewiring through reduced RTK shedding represents a surprising mechanism for bypass signaling in cancer drug resistance.
SIGNIFICANCE: Genetic, epigenetic, and gene expression alterations often fail to explain adaptive drug resistance in cancer. This work presents a novel post-translational mechanism of such resistance: Kinase inhibitors, particularly targeting MAPK signaling, increase tumor cell surface receptor levels due to widely reduced proteolysis, allowing tumor signaling to circumvent intended drug action.

Halberg N, Sengelaub CA, Navrazhina K, et al.
PITPNC1 Recruits RAB1B to the Golgi Network to Drive Malignant Secretion.
Cancer Cell. 2016; 29(3):339-53 [PubMed] Free Access to Full Article Related Publications
Enhanced secretion of tumorigenic effector proteins is a feature of malignant cells. The molecular mechanisms underlying this feature are poorly defined. We identify PITPNC1 as a gene amplified in a large fraction of human breast cancer and overexpressed in metastatic breast, melanoma, and colon cancers. Biochemical, molecular, and cell-biological studies reveal that PITPNC1 promotes malignant secretion by binding Golgi-resident PI4P and localizing RAB1B to the Golgi. RAB1B localization to the Golgi allows for the recruitment of GOLPH3, which facilitates Golgi extension and enhanced vesicular release. PITPNC1-mediated vesicular release drives metastasis by increasing the secretion of pro-invasive and pro-angiogenic mediators HTRA1, MMP1, FAM3C, PDGFA, and ADAM10. We establish PITPNC1 as a PI4P-binding protein that enhances vesicular secretion capacity in malignancy.

Wu X, Tang H, Liu G, et al.
miR-448 suppressed gastric cancer proliferation and invasion by regulating ADAM10.
Tumour Biol. 2016; 37(8):10545-51 [PubMed] Related Publications
MicroRNAs (miRNAs) are a class of short, noncoding RNAs that act a crucial role in tumor development. Previous studies showed that miR-448 expression was deregulated in many tumors. However, the role of miR-448 in gastric cancer (GC) remains unknown. In our study, we demonstrated that miR-448 expression was downregulated in GC tissues compared with the corresponding nontumor tissues. We also showed that miR-448 expression was downregulated in GC cell lines. Ectopic expression of miR-448 suppressed GC cell proliferation, colony formation, and invasion. Moreover, we identified A Disintegrin And Metalloproteinases 10 (ADAM10) as a direct target gene of miR-448 in GC cell. ADAM10 expression was upregulated in GC tissues and cells. Furthermore, the expression level of miR-448 was negatively correlated with the expression level of ADAM10 in GC tissues. Moreover, ADAM10 overexpression rescued the effect of miR-448-mediated GC cell proliferation, colony formation, and invasion. These results demonstrated that miR-448 might play as a tumor suppressor miRNA partly through targeting ADAM10 expression.

Jing P, Sa N, Liu X, et al.
MicroR-140-5p suppresses tumor cell migration and invasion by targeting ADAM10-mediated Notch1 signaling pathway in hypopharyngeal squamous cell carcinoma.
Exp Mol Pathol. 2016; 100(1):132-8 [PubMed] Related Publications
MicroRNAs (miRNAs) are small non-coding RNAs of approximately 22 nucleotides that negatively regulate gene expression at the post-transcriptional level. Downexpression of miR-140-5p was reported in some human cancers, and combined with a reduction of cell migration and invasion, suggesting that miR-140-5p functions as a tumor suppressor. However, little is known about the expression and function of miR-140-5p in hypopharyngeal squamous cell carcinoma (HSCC). In this research, we found that miR-140-5p was significantly downregulated in HSCC tissues and correlated to tumor classification and lymph node metastasis. Restoration of miR-140-5p suppressed the migration and invasion of FaDu cells, and decreased the protein expression levels of ADAM10. Furthermore, the luciferase reporter assay revealed that miR-140-5p was directly bound to ADAM10 mRNA and knockdown of ADAM10 could inhibit FaDu cell migration and invasion and reduced the protein expression levels of and Notch1 intracellular domain (NICD1). Of note, knockdown of Notch1 could inhibit the migration and invasion of FaDu cells and rescued the effect of miR-140-5p inhibitor in FaDu cells. Taken together, our study demonstrates that miR-140-5p suppresses tumor migration and invasion by inhibiting ADAM10-mediated Notch1 signaling pathway and suggests that miR-140-5p could have potential therapeutic applications in HSCC.

D'Asti E, Huang A, Kool M, et al.
Tissue Factor Regulation by miR-520g in Primitive Neuronal Brain Tumor Cells: A Possible Link between Oncomirs and the Vascular Tumor Microenvironment.
Am J Pathol. 2016; 186(2):446-59 [PubMed] Related Publications
Pediatric embryonal brain tumors with multilayered rosettes demonstrate a unique oncogenic amplification of the chromosome 19 miRNA cluster, C19MC. Because oncogenic lesions often cause deregulation of vascular effectors, including procoagulant tissue factor (TF), this study explores whether there is a link between C19MC oncogenic miRNAs (oncomirs) and the coagulant properties of cancer cells, a question previously not studied. In a pediatric embryonal brain tumor tissue microarray, we observed an association between C19MC amplification and reduced fibrin content and TF expression, indicative of reduced procoagulant activity. In medulloblastoma cell lines (DAOY and UW228) engineered to express miR-520g, a biologically active constituent of the C19MC cluster, we observed reduced TF expression, procoagulant and TF signaling activities (responses to factor VIIa stimulation), and diminished TF emission as cargo of extracellular vesicles. Antimir and luciferase reporter assays revealed a specific and direct effect of miR-520g on the TF 3' untranslated region. Although the endogenous MIR520G locus is methylated in differentiated cells, exposure of DAOY cells to 5-aza-2'-deoxycytidine or their growth as stem cell-like spheres up-regulated endogenous miR-520g with a coincident reduction in TF expression. We propose that the properties of tumors harboring oncomirs may include unique alterations of the vascular microenvironment, including deregulation of TF, with a possible impact on the biology, therapy, and hemostatic adverse effects of both disease progression and treatment.

Woods N, Trevino J, Coppola D, et al.
Fendiline inhibits proliferation and invasion of pancreatic cancer cells by interfering with ADAM10 activation and β-catenin signaling.
Oncotarget. 2015; 6(34):35931-48 [PubMed] Free Access to Full Article Related Publications
ADAM10 (A Disintegrin and Metalloprotease Domain 10) affects the pathophysiology of various cancers, and we had shown that inhibition of ADAM10 sensitizes pancreatic cancer cells to gemcitabine. ADAM10 is activated in response to calcium influx, and here we examined if calcium channel blockers (CCB) would impede ADAM10 activation and affect biology of pancreatic cancer cells. We find that the CCB, fendiline, significantly reduces proliferation, migration, invasion, and anchorage independent growth of pancreatic cancer cells. This was associated with ADAM10 inhibition and its localization at the actin-rich membrane protrusions. Further, fendiline-treated cells formed cadherin-catenin positive tight adherens junctions and elicited defective protein trafficking and recycling. Furthermore, the expression of β-catenin target genes, cyclinD1, c-Myc and CD44, were significantly decreased, suggesting that fendiline might prevent cell proliferation and migration by inhibiting ADAM10 function, cadherin proteolysis and stabilization of cadherin-catenin interaction at the plasma membrane. This will subsequently diminish β-catenin intracellular signaling and repress TCF/LEF target gene expression. Supporting this notion, RNAi-directed downregulation of ADAM10 in cancer cells decreased the expression of cyclinD1, c-Myc and CD44. Furthermore, analysis of human pancreatic tumor tissue microarrays and lysates showed elevated levels of ADAM10, suggesting that aberrant activation of ADAM10 plays a fundamental role in growth and metastasis of PDACs and inhibiting this pathway might be a viable strategy to combat PDACs.

Cai ZX, Guo HS, Wang C, et al.
Double-Edged Roles of Nitric Oxide Signaling on APP Processing and Amyloid-β Production In Vitro: Preliminary Evidence from Sodium Nitroprusside.
Neurotox Res. 2016; 29(1):21-34 [PubMed] Related Publications
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is thought to be caused in part by the age-related accumulation of amyloid-β (Aβ) in the brain. Recent findings have revealed that nitric oxide (NO) modulates the processing of amyloid-β precursor protein (APP) and alters Aβ production; however, the previously presented data are contradictory and the underlying molecular mechanisms are still incomplete. Here, using human SH-SY5Y neuroblastoma cells stably transfected with wild-type APPwt695, we found that NO, derived from NO donor sodium nitroprusside (SNP), bi-directionally modulates APP processing in vitro. The data from ELISA and Western blot (WB) tests indicated that SNP at lower concentrations (0.01 and 0.1 μM) inhibits BACE1 expression, thus consequently suppresses APP β-cleavage and decreases Aβ production. In contrast, SNP at higher concentrations (10 and 20 μM) biases the APP processing toward the amyloidogenic pathway as evidenced by an increased BACE1 but a decreased ADAM10 expression, together with an elevated Aβ secretion. This bi-directional modulating activity of SNP on APP processing was completely blocked by specific NO scavenger c-PTIO, indicating NO-dependent mechanisms. Moreover, the anti-amyloidogenic activity of SNP is sGC/cGMP/PKG-dependent as evidenced by its reversal by sGC/PKG inhibitions, whereas the amyloidogenic activity of SNP is peroxynitrite-related and can be reversed by peroxynitrite scavenger uric acid. In summary, these present findings predict a double-edged role of NO in APP processing in vitro. Low (physiological) levels of NO inhibit the amyloidogenic processing of APP, whereas extra-high (pathological) concentrations of NO favor the amyloidogenic pathway of APP processing. This preliminary study may provide further evidence to clarify the molecular roles of NO and NO-related signaling in AD and supply potential molecular targets for AD treatment.

Fang Y, Garnier D, Lee TH, et al.
PML-RARa modulates the vascular signature of extracellular vesicles released by acute promyelocytic leukemia cells.
Angiogenesis. 2016; 19(1):25-38 [PubMed] Related Publications
Oncogenic transformation is believed to impact the vascular phenotype and microenvironment in cancer, at least in part, through mechanisms involving extracellular vesicles (EVs). We explored these questions in the context of acute promyelocytic leukemia cells (NB4) expressing oncogenic fusion protein, PML-RARa and exquisitely sensitive to its clinically used antagonist, the all-trans retinoic acid (ATRA). We report that NB4 cells produce considerable numbers of EVs, which are readily taken up by cultured endothelial cells triggering their increased survival. NB4 EVs contain PML-RARa transcript, but no detectable protein, which is also absent in endothelial cells upon the vesicle uptake, thereby precluding an active intercellular trafficking of this oncogene in this setting. ATRA treatment changes the emission profile of NB4-related EVs resulting in preponderance of smaller vesicles, an effect that occurs in parallel with the onset of cellular differentiation. ATRA also increases IL-8 mRNA and protein content in NB4 cells and their EVs, while decreasing the levels of VEGF and tissue factor (TF). Endothelial cell uptake of NB4-derived EVs renders these cells more TF-positive and procoagulant, and this effect is diminished by pre-treatment of EV donor cells with ATRA. Profiling angiogenesis-related transcripts in intact and ATRA-treated APL cells and their EVs reveals multiple differences attributable to cellular responses and EV molecular packaging. These observations point to the potential significance of changes in the angiogenic signature and activity associated with EVs released from tumor cells subjected to targeted therapy.

Hachim IY, Hachim MY, Lopez VM, et al.
Prolactin Receptor Expression is an Independent Favorable Prognostic Marker in Human Breast Cancer.
Appl Immunohistochem Mol Morphol. 2016; 24(4):238-45 [PubMed] Related Publications
Prolactin (PRL) hormone plays an important role in the development of the mammary gland and terminal differentiation of the mammary epithelial cells. While initial studies suggested that PRL may contribute to the development of breast cancer through PRL/prolactin receptor (PRLR) autocrine function, mounting evidence indicate a different role for PRL, highlighting this hormone as a regulator of epithelial plasticity and as a potential tumor suppressor. To gain further insights into the role of PRL in human breast carcinogenesis, immunohistochemistry analyses of PRLR protein expression levels using tissue microarray of 102 cases were done in comparison with various clinical/pathologic parameters and molecular subtypes. In addition, gene expression level of PRLR was also evaluated in relation to intrinsic molecular subtypes, tumor grade, and patient outcome using GOBO database for 1881 breast cancer patients. Interestingly, PRLR expression was found to be significantly downregulated in invasive breast cancer (21.4%) in comparison with normal/benign (80%) and in situ carcinoma (60%) (P=0.003498). Moreover, PRLR expression was associated with lymph node negativity and low-grade well-differentiated tumors. PRLR expression was strongest in luminal A subtype, and was virtually undetectable in the worse prognosis triple-negative breast cancer subtype (P=0.00001). Furthermore, PRLR expression was independent of ER, PR, HER-2, and P53 status. Finally, PRLR expression was significantly (P<0.01) associated with prolonged distant metastasis-free survival in breast cancer patients. In conclusion, our results highlight PRLR as an independent predictor of favorable prognosis in human breast cancer.

Mullooly M, McGowan PM, Kennedy SA, et al.
ADAM10: a new player in breast cancer progression?
Br J Cancer. 2015; 113(6):945-51 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The ADAM proteases are best known for their role in shedding the extracellular domain of transmembrane proteins. Among the transmembrane proteins shed by ADAM10 are notch, HER2, E-cadherin, CD44, L1 and the EGFR ligands, EGF and betacellulin. As cleavage of several of these proteins has been implicated in cancer formation and progression, we hypothesised that ADAM10 is also involved in these processes.
METHODS: ADAM10 expression was decreased by RNA interference and the effects of this on cell numbers, invasion and migration were determined. We also examined the effect of ADAM10 inhibition on breast cancer cell line invasion and migration.
RESULTS: Using the triple-negative (TN) breast cancer cell lines, BT20, MDA-MB-231 and the non-TN cell line MDA-MB-453, knockdown of ADAM10 expression significantly decreased in vitro migration (P<0.01; for each cell line). Similarly, treatment with the ADAM10-selective inhibitor GI254023X reduced migration in the three cell lines (for BT20, P<0.001; for MDA-MB-231, P=0.005; for MDA-MB-453, P=0.023). In contrast, neither knockdown of ADAM10 nor treatment with the ADAM10-selective inhibitor GI254023X significantly affected cell numbers. Using extracts of primary breast cancers, higher levels of ADAM10 were found more frequently in high-grade vs low-grade tumours (P<0.001) and in oestrogen receptor (ER)-negative compared with ER-positive tumours (P=0.005). Analysis of pooled publicly available data sets found that high levels of ADAM10 mRNA were associated with adverse outcome in patients with the basal subtype of breast cancer.
CONCLUSIONS: Based on our combined cell line and breast cancer extract data, we conclude that ADAM10 is likely to be involved in breast cancer progression, especially in the basal subtype.

Qiu H, Tang X, Ma J, et al.
Notch1 Autoactivation via Transcriptional Regulation of Furin, Which Sustains Notch1 Signaling by Processing Notch1-Activating Proteases ADAM10 and Membrane Type 1 Matrix Metalloproteinase.
Mol Cell Biol. 2015; 35(21):3622-32 [PubMed] Free Access to Full Article Related Publications
Notch1 is an evolutionarily conserved transmembrane receptor involved in melanoma growth. Notch1 is first cleaved by furin in the Golgi apparatus to produce the biologically active heterodimer. Following ligand binding, Notch1 is cleaved at the cell membrane by proteases such as ADAM10 and -17 and membrane type 1 matrix metalloproteinase (MT1-MMP), the latter of which we recently identified as a novel protease involved in Notch1 processing. The final cleavage is γ-secretase dependent and releases the active Notch intracellular domain (NIC). We now demonstrate that Notch1 directly regulates furin expression. Aside from activating Notch1, furin cleaves and activates several proteases, including MT1-MMP, ADAM10, and ADAM17. By chromatin immunoprecipitation and a reporter assay, we demonstrate that Notch1 binds at position -1236 of the furin promoter and drives furin expression. The Notch1-dependent enhancement of furin expression increases the activities of MT1-MMP and ADAM10 but not that of ADAM17, as demonstrated by short hairpin RNA (shRNA) knockdown of furin, and promotes the cleavage of Notch1 itself. These data highlight a novel positive-feedback loop whereby Notch1-dependent furin expression can induce Notch1 signaling by increasing Notch1 processing and by potentiating the activity of the proteases responsible for Notch1 activation. This leads to Notch1 signal amplification, which can promote melanoma tumor growth and progression, as demonstrated by the inhibition of cell migration and invasion upon furin inhibition downstream of Notch1. Disruption of such feedback signaling might represent an avenue for the treatment of melanoma.

Bonetta AC, Mailly L, Robinet E, et al.
Artificial microRNAs against the viral E6 protein provoke apoptosis in HPV positive cancer cells.
Biochem Biophys Res Commun. 2015; 465(4):658-64 [PubMed] Related Publications
High-risk human papillomavirus (HPV) types 16 and 18 are associated with more than 70% of cervical cancer cases. The oncoprotein E6 is multifunctional and has numerous cellular partners. The best-known activity of E6 is the polyubiquination of the pro-apoptotic tumor suppressor p53, targeting it for degradation by the 26S proteasome. Loss of p53 triggers genomic instability and favors cancer development. Here, we generated recombinant adenovirus (Ad) vectors expressing artificial microRNAs directed against HPV16 E6 (Ad16_1) or HPV18 E6 (Ad18_2). E6-knockdown was observed in HeLa after treatment with Ad18_2 and in SiHa with Ad16_1. Western-blot experiments found an increase in p53 levels after treatment in both cell lines. Cell death was observed in both cell lines after knockdown of E6. Further analysis such as cleavage of caspases (3 and 7) as well as of PARP1 indicated that treated HeLa and SiHa cells underwent apoptosis. The growth of HeLa-derived tumors developed in nude mice was significantly reduced after intra-tumoral injection of Ad18_2. Therefore, vectorisation of artificial miRNA against E6 oncoprotein by means of recombinant adenoviruses might represent a valuable therapeutic approach for treating HPV-positive cancers.

Lee TH, Chennakrishnaiah S, Rak J
Oncogene-dependent survival of highly transformed cancer cells under conditions of extreme centrifugal force - implications for studies on extracellular vesicles.
Cell Mol Biol Lett. 2015; 20(1):117-29 [PubMed] Related Publications
Extracellular vesicles (EVs), including exosomes, are a subject of intense interest due to their emission by cancer cells and role in intercellular communication. Earlier reports suggested that oncogenes, such as RAS, MET or EGFR, drive cellular vesiculation. Interestingly, these oncogenes may also traffic between cells using the EV-mediated emission and uptake processes. One of the main tools in the analysis of EVs are ultracentrifugation protocols designed to efficiently separate parental cells from vesicles through a sequence of steps involving increasing g-force. Here we report that ultracentrifugationonly EV preparations from highly transformed cancer cells, driven by the overexpression of oncogenic H-ras (RAS-3) and v-src (SRC-3), may contain clonogenic cancer cells, while preparations of normal or less aggressive human cell lines are generally free from such contamination. Introduction of a filtration step eliminates clonogenic cells from the ultracentrifugate. The survival of RAS-3 and SRC-3 cells under extreme conditions of centrifugal force (110,000 g) is oncogene-induced, as EV preparations of their parental non-tumourigenic cell line (IEC-18) contain negligible numbers of clonogenic cells. Moreover, treatment of SRC-3 cells with the SRC inhibitor (PP2) markedly reduces the presence of such cells in the unfiltered ultracentrifugate. These observations enforce the notion that EV preparations require careful filtration steps, especially in the case of material produced by highly transformed cancer cell types. We also suggest that oncogenic transformation may render cells unexpectedly resistant to extreme physical forces, which may affect their biological properties in vivo.

Pyysalo S, Ohta T, Rak R, et al.
Overview of the Cancer Genetics and Pathway Curation tasks of BioNLP Shared Task 2013.
BMC Bioinformatics. 2015; 16 Suppl 10:S2 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Since their introduction in 2009, the BioNLP Shared Task events have been instrumental in advancing the development of methods and resources for the automatic extraction of information from the biomedical literature. In this paper, we present the Cancer Genetics (CG) and Pathway Curation (PC) tasks, two event extraction tasks introduced in the BioNLP Shared Task 2013. The CG task focuses on cancer, emphasizing the extraction of physiological and pathological processes at various levels of biological organization, and the PC task targets reactions relevant to the development of biomolecular pathway models, defining its extraction targets on the basis of established pathway representations and ontologies.
RESULTS: Six groups participated in the CG task and two groups in the PC task, together applying a wide range of extraction approaches including both established state-of-the-art systems and newly introduced extraction methods. The best-performing systems achieved F-scores of 55% on the CG task and 53% on the PC task, demonstrating a level of performance comparable to the best results achieved in similar previously proposed tasks.
CONCLUSIONS: The results indicate that existing event extraction technology can generalize to meet the novel challenges represented by the CG and PC task settings, suggesting that extraction methods are capable of supporting the construction of knowledge bases on the molecular mechanisms of cancer and the curation of biomolecular pathway models. The CG and PC tasks continue as open challenges for all interested parties, with data, tools and resources available from the shared task homepage.

Panmanee J, Nopparat C, Chavanich N, et al.
Melatonin regulates the transcription of βAPP-cleaving secretases mediated through melatonin receptors in human neuroblastoma SH-SY5Y cells.
J Pineal Res. 2015; 59(3):308-20 [PubMed] Related Publications
Melatonin is involved in the control of various physiological functions, such as sleep, cell growth and free radical scavenging. The ability of melatonin to behave as an antioxidant, together with the fact that the Alzheimer-related amyloid β-peptide (Aβ) triggers oxidative stress through hydroxyl radical-induced cell death, suggests that melatonin could reduce Alzheimer's pathology. Although the exact etiology of Alzheimer's disease (AD) remains to be established, excess Aβ is believed to be the primary contributor to the dysfunction and degeneration of neurons that occurs in AD. Aβ peptides are produced via the sequential cleavage of β-secretase β-site APP-cleaving enzyme 1 (BACE1) and γ-secretase (PS1/PS2), while α-secretase (ADAM10) prevents the production of Aβ peptides. We hypothesized that melatonin could inhibit BACE1 and PS1/PS2 and enhance ADAM10 expression. Using the human neuronal SH-SY5Y cell line, we found that melatonin inhibited BACE1 and PS1 and activated ADAM10 mRNA level and protein expression in a concentration-dependent manner and mediated via melatonin G protein-coupled receptors. Melatonin inhibits BACE1 and PS1 protein expressions through the attenuation of nuclear factor-κB phosphorylation (pNF-κB). Moreover, melatonin reduced BACE1 promoter transactivation and consequently downregulated β-secretase catalytic activity. The present data show that melatonin is not only a potential regulator of β/γ-secretase but also an activator of α-secretase expression through the activation of protein kinase C, thereby favoring the nonamyloidogenic pathway over the amyloidogenic pathway. Altogether, our findings suggest that melatonin may be a potential therapeutic agent for reducing the risk of AD in humans.

Scherzed A, Hackenberg S, Froelich K, et al.
Effects of salinomycin and CGP37157 on head and neck squamous cell carcinoma cell lines in vitro.
Mol Med Rep. 2015; 12(3):4455-61 [PubMed] Related Publications
Surgery, radiation, chemotherapy or a combinations of these are all accepted modalities for the treatment of head and neck squamous cell carcinoma (HNSCC). Despite this, 40‑60% of patients suffering from HNSCC develop loco‑regional failure and/or distant metastases. Salinomycin has been demonstrated to be >100‑fold more effective than paclitaxel at causing cancer stem cell death, therefore, it may offer an important improvement in cancer therapy. However, the toxicity of salinomycin is of concern. A possible solution may be the administration of additive drugs, which reduce the toxicity. By inhibiting the mitochondrial Na+/Ca2+ exchanger using the benzodiazepine derivate, CGP37157 (CGP), a significant reduction in salinomycin neuronal toxicity has been observed. This raises the question of whether CGP also inhibits the tumor toxicity of salinomycin. In the present study, the FaDu and HLaC79 C1 HNSCC cell lines were treated with salinomycin with or without CGP. Comparative viability assessments were performed using microscopy, a fluorescein diacetate assay, an MTT assay, a clonogenic assay and annexin V‑propidium iodide staining. The expression levels of MDR‑1 were monitored using reverse transcription‑quantitative polymerase chain reaction. Salinomycin alone, and in combination with CGP, achieved a significant attenuation of cell viability and increased apoptosis in a dose‑dependent manner. However, the tumor toxicity of salinomycin was not inhibited by CGP. The HLaC79 C1 cells were more sensitive to salinomycin, compared with the FaDu cells, with this sensitivity being due to high expression levels of MDR‑1 by the HLaC79 C1 cells. In conclusion, CGP did not counteract the tumor toxicity of salinomycin in vitro and may be a promising drug in future anticancer therapy. The results of the present study encourages further investigation of the toxicological aspects of salinomycin, particularly in human cells and animal models.

Zingoni A, Cecere F, Vulpis E, et al.
Genotoxic Stress Induces Senescence-Associated ADAM10-Dependent Release of NKG2D MIC Ligands in Multiple Myeloma Cells.
J Immunol. 2015; 195(2):736-48 [PubMed] Related Publications
Genotoxic stress can promote antitumor NK cell responses by upregulating the surface expression of activating ligands on cancer cells. Moreover, a number of studies suggested a role for soluble NK group 2D ligands in the impairment of NK cell tumor recognition and killing. We investigated whether genotoxic stress could promote the release of NK group 2D ligands (MHC class I-related chain [MIC]A and MICB), as well as the molecular mechanisms underlying this event in human multiple myeloma (MM) cells. Our results show that genotoxic agents used in the therapy of MM (i.e., doxorubicin and melphalan) selectively affect the shedding of MIC molecules that are sensitive to proteolytic cleavage, whereas the release of the short MICA*008 allele, which is frequent in the white population, is not perturbed. In addition, we found that a disintegrin and metalloproteinase 10 expression is upregulated upon chemotherapeutic treatment both in patient-derived CD138(+)/CD38(+) plasma cells and in several MM cell lines, and we demonstrate a crucial role for this sheddase in the proteolytic cleavage of MIC by means of silencing and pharmacological inhibition. Interestingly, the drug-induced upregulation of a disintegrin and metalloproteinase 10 on MM cells is associated with a senescent phenotype and requires generation of reactive oxygen species. Moreover, the combined use of chemotherapeutic drugs and metalloproteinase inhibitors enhances NK cell-mediated recognition of MM cells, preserving MIC molecules on the cell surface and suggesting that targeting of metalloproteinases in conjunction with chemotherapy could be exploited for NK cell-based immunotherapeutic approaches, thus contributing to avoid the escape of malignant cells from stress-elicited immune responses.

Scherzad A, Steber M, Gehrke T, et al.
Human mesenchymal stem cells enhance cancer cell proliferation via IL-6 secretion and activation of ERK1/2.
Int J Oncol. 2015; 47(1):391-7 [PubMed] Related Publications
Human mesenchymal stem cells (hMSC) are frequently used in tissue engineering. Due to their strong tumor tropism, hMSC seem to be a promising vehicle for anticancer drugs. However, interactions between hMSC and cancer are ambiguous. Particularly the cytokines and growth factors seem to play an important role in cancer progression and metastasis. The present study evaluated the effects of hMSC on head and neck squamous cell carcinoma (HNSCC) cell lines (FaDu and HLaC78) in vitro. hMSC released several cytokines and growth factors. FaDu and HLaC78 showed a significant enhancement of cell proliferation after cultivation with hMSC-conditioned medium as compared to control. This proliferation improvement was inhibited by the addition of anti-IL-6. The western blot showed an activation of Erk1/2 in FaDu and HLaC78 by hMSC-conditioned medium. HNSCC cell lines expressed EGFR. The current study confirms the importance of cytokines secreted by hMSC in cancer biology. Especially IL-6 seems to play a key role in cancer progression. Thus, the use of hMSC as a carrier for cancer therapy must be discussed critically. Future studies should evaluate the possibility of generating genetically engineered hMSC with, for example, the absence of IL-6 secretion.

Rakkeitwinai S, Lursinsap C, Aporntewan C, Mutirangura A
New feature selection for gene expression classification based on degree of class overlap in principal dimensions.
Comput Biol Med. 2015; 64:292-8 [PubMed] Related Publications
Micro-array data are typically characterized by high dimensional features with a small number of samples. Several problems in identifying genes causing diseases from micro-array data can be transformed into the problem of classifying the features extracted from gene expression in micro-array data. However, too many features can cause low prediction accuracy as well as high computational complexity. Dimensional reduction is a method to eliminate irrelevant features to improve the prediction accuracy. Typically, the eigenvalues or dimensional data variance from principal component analysis are used as criteria to select relevant features. This approach is simple but not efficient since it does not concern the degree of data overlap in each dimension in the feature space. A new method to select relevant features based on degree of dimensional data overlap with proper feature selection was introduced. Furthermore, our study concentrated on small sized data sets which usually occur in reality. The experimental results signified that this new approach can achieve substantially higher prediction accuracy when compared with other methods.

Magnus N, Meehan B, Garnier D, et al.
The contribution of tumor and host tissue factor expression to oncogene-driven gliomagenesis.
Biochem Biophys Res Commun. 2014; 454(2):262-8 [PubMed] Related Publications
Glioblastoma multiforme (GBM) is an aggressive form of glial brain tumors, associated with angiogenesis, thrombosis, and upregulation of tissue factor (TF), the key cellular trigger of coagulation and signaling. Since TF is upregulated by oncogenic mutations occurring in different subsets of human brain tumors we investigated whether TF contributes to tumourigenesis driven by oncogenic activation of EGFR (EGFRvIII) and RAS pathways in the brain. Here we show that TF expression correlates with poor prognosis in glioma, but not in GBM. In situ, the TF protein expression is heterogeneously expressed in adult and pediatric gliomas. GBM cells harboring EGFRvIII (U373vIII) grow aggressively as xenografts in SCID mice and their progression is delayed by administration of monoclonal antibodies blocking coagulant (CNTO 859) and signaling (10H10) effects of TF in vivo. Mice in which TF gene is disrupted in the neuroectodermal lineage exhibit delayed progression of spontaneous brain tumors driven by oncogenic N-ras and SV40 large T antigen (SV40LT) expressed under the control of sleeping beauty transposase. Reduced host TF levels in low-TF/SCID hypomorphic mice mitigated growth of glioma subcutaneously but not in the brain. Thus, we suggest that tumor-associated TF may serve as therapeutic target in the context of oncogene-driven disease progression in a subset of glioma.

Deng G, Shen J, Yin M, et al.
Selective inhibition of mutant isocitrate dehydrogenase 1 (IDH1) via disruption of a metal binding network by an allosteric small molecule.
J Biol Chem. 2015; 290(2):762-74 [PubMed] Free Access to Full Article Related Publications
Cancer-associated point mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) confer a neomorphic enzymatic activity: the reduction of α-ketoglutarate to d-2-hydroxyglutaric acid, which is proposed to act as an oncogenic metabolite by inducing hypermethylation of histones and DNA. Although selective inhibitors of mutant IDH1 and IDH2 have been identified and are currently under investigation as potential cancer therapeutics, the mechanistic basis for their selectivity is not yet well understood. A high throughput screen for selective inhibitors of IDH1 bearing the oncogenic mutation R132H identified compound 1, a bis-imidazole phenol that inhibits d-2-hydroxyglutaric acid production in cells. We investigated the mode of inhibition of compound 1 and a previously published IDH1 mutant inhibitor with a different chemical scaffold. Steady-state kinetics and biophysical studies show that both of these compounds selectively inhibit mutant IDH1 by binding to an allosteric site and that inhibition is competitive with respect to Mg(2+). A crystal structure of compound 1 complexed with R132H IDH1 indicates that the inhibitor binds at the dimer interface and makes direct contact with a residue involved in binding of the catalytically essential divalent cation. These results show that targeting a divalent cation binding residue can enable selective inhibition of mutant IDH1 and suggest that differences in magnesium binding between wild-type and mutant enzymes may contribute to the inhibitors' selectivity for the mutant enzyme.

Heo W, Lee YS, Son CH, et al.
Radiation-induced matrix metalloproteinases limit natural killer cell-mediated anticancer immunity in NCI-H23 lung cancer cells.
Mol Med Rep. 2015; 11(3):1800-6 [PubMed] Related Publications
Radiotherapy has been used to treat cancer for >100 years and is required by numerous patients with cancer. Ionizing radiation effectively inhibits the growth of cancer cells by inducing cell death and increasing anticancer immunity, through the induction of natural killer group 2 member D ligands (NKG2DLs); however, adverse effects have also been reported, including the promotion of metastasis. Matrix metalloproteinases (MMPs) are induced by ionizing radiation and have an important role in the invasion and metastasis of cancer cells. Previously, MMPs were demonstrated to increase the shedding of NKG2DLs, which may reduce the surface expression of NKG2DLs on cancer cells. As a consequence, the cancer cells may escape natural killer (NK)‑mediated anticancer immunity. In the present study, NCI‑H23 human non‑small cell lung cancer cells were used to investigate the combined effects of ionizing radiation and MMP inhibitors on the expression levels of NKG2DLs. Ionizing radiation increased the expression of MMP2 and ADAM metalloproteinase domain 10 protease, as well as NKG2DLs. The combined treatment of ionizing radiation and MMP inhibitors increased the surface expression levels of NKG2DLs and resulted in the increased susceptibility of the cancer cells to NK‑92 natural killer cells. Furthermore, soluble NKG2DLs were increased in the media by ionizing radiation and blocked by MMP inhibitors. The present study suggests that radiotherapy may result in the shedding of soluble NKG2DLs, through the induction of MMP2, and combined treatment with MMP inhibitors may minimize the adverse effects of radiotherapy.

Shao Y, Sha XY, Bai YX, et al.
Effect of A disintegrin and metalloproteinase 10 gene silencing on the proliferation, invasion and migration of the human tongue squamous cell carcinoma cell line TCA8113.
Mol Med Rep. 2015; 11(1):212-8 [PubMed] Free Access to Full Article Related Publications
The present study aimed to investigate the effect of A disintegrin and metalloproteinase 10 (ADAM10) gene silencing on the proliferation, migration and invasion of the human tongue squamous cell carcinoma cell line TCA8113. RNA interference was used to knock down the expression of ADAM10 in the TCA8113 cell line and the proliferation, migration and invasive ability of the treated cells were observed in vitro. The expression levels of epidermal growth factor receptor (EGFR) and E-cadherin in the treated cells were determined by western blot analysis. The proliferation, migration and invasion abilities of cells in the ADAM10 siRNA-treated group were significantly lower than those in the control groups (P<0.05). In addition, compared with the control groups, the expression levels of EGFR and E-cadherin in the ADAM10 siRNA-treated cells were significantly decreased (P<0.05) and increased (P<0.05), respectively. These results suggested that ADAM10 is important in regulating the proliferation, invasion and migration of the human tongue squamous cell carcinoma cell line TCA8113 and that the mechanism may, at least in part, be associated with the upregulation of EGFR and the downregulation of E-cadherin.

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

Cite this page: Cotterill SJ. ADAM10, Cancer Genetics Web: http://www.cancer-genetics.org/ADAM10.htm 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: 11 March, 2017     Cancer Genetics Web, Established 1999