title: Snail regulates the motility of oral cancer cells via RhoA/Cdc42/p-ERM pathway.
abstract: The transcriptional factor Snail has been reported to possess properties related to cancer progression; however, the mechanism for it is not fully understood. Our data showed that Snail knockdown by small interfering RNA in two OSCC cell lines, WSU-HN6 and CAL27, significantly inhibited cell migration and invasion which also resulted in decreased cell motility, such as impaired cell spreading on type I collagen substrate, reduced filopodia, and premature assembly of stress fibers. In addition, Snail-silencing decreased Cdc42 activity but increased RhoA activity, accompanied by the downregulation in both p-ERM expression and cell motility. Meanwhile, endogenous p-ERM was found specifically co-precipitated with activated Cdc42, but not RhoA, and this co-association was decreased by Snail-silencing. The small molecule inhibitors of Rho-associated kinase (Y27632) markedly enhanced Cdc42 activity and the association of p-ERM with activated Cdc42, increasing cell motility remarkably. Using immunohistochemistry, Snail and p-ERM overexpressions were found in OSCC tissues correlated with nodal metastasis and shorter survival. Taken together, these results demonstrate that Snail regulates cell motility through RhoA/Cdc42/p-ERM pathway and may serve as a biomarker to predict prognosis for OSCC patients. Although RhoA and Cdc42 are concurrently regulated downstream of Snail, there is a direct interplay between them, which indicates RhoA has to be inactivated at some point in cell motility cycle.
authors.affiliation: Department of Oral Pathology, Peking University School and Hospital of Stomatology, Beijing, PR China.
authors.forename: Yao-Yin
authors.initials: YY
authors.lastname: Li
authors.affiliation: Department of Oral Pathology, Peking University School and Hospital of Stomatology, Beijing, PR China. Electronic address: zhoucx2008@126.com.
authors.forename: Chuan-Xiang
authors.initials: CX
authors.lastname: Zhou
authors.affiliation: Department of Oral Pathology, Peking University School and Hospital of Stomatology, Beijing, PR China. Electronic address: gaoyan0988@163.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gao
mesh_terms: D000368:Aged; D000577:Amides / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D010766:Phosphorylation; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D016019:Survival Analysis; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000235:genetics* / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
chemical_list: D000577:Amides; D004268:DNA-Binding Proteins; C086680:ETV5 protein, human; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D034741:RNA, Small Interfering; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C066737:RHOA protein, human; C108830:Y 27632; D020764:cdc42 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein
keywords: Cell motility; Epithelial-to-mesenchymal transition; Metastasis; Oral squamous cell carcinoma; RhoA/Cdc42/p-ERM pathway; Snail