title: Inhibition of TMEM16A expression suppresses growth and invasion in human colorectal cancer cells.
abstract: Metastasis leads to poor prognosis in colorectal cancer patients, and there is a growing need for new therapeutic targets. TMEM16A (ANO1, DOG1 or TAOS2) has recently been identified as a calcium-activated chloride channel (CaCC) and is reported to be overexpressed in several malignancies; however, its expression and function in colorectal cancer (CRC) remains unclear. In this study, we found expression of TMEM16A mRNA and protein in high-metastatic-potential SW620, HCT116 and LS174T cells, but not in primary HCT8 and SW480 cells, using RT-PCR, western blotting and immunofluorescence labeling. Patch-clamp recordings detected CaCC currents regulated by intracellular Ca(2+) and voltage in SW620 cells. Knockdown of TMEM16A by short hairpin RNAs (shRNA) resulted in the suppression of growth, migration and invasion of SW620 cells as detected by MTT, wound-healing and transwell assays. Mechanistically, TMEM16A depletion was accompanied by the dysregulation of phospho-MEK, phospho-ERK1/2 and cyclin D1 expression. Flow cytometry analysis showed that SW620 cells were inhibited from the G1 to S phase of the cell cycle in the TMEM16A shRNA group compared with the control group. In conclusion, our results indicate that TMEM16A CaCC is involved in growth, migration and invasion of metastatic CRC cells and provide evidence for TMEM16A as a potential drug target for treating metastatic colorectal carcinoma.
authors.affiliation: Key Laboratory for Molecular and Chemical Genetics of Critical Human Diseases of Jilin Province, Jilin University Bethune Second Hospital, Changchun, P. R. China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Sui
authors.affiliation: Key Laboratory for Molecular and Chemical Genetics of Critical Human Diseases of Jilin Province, Jilin University Bethune Second Hospital, Changchun, P. R. China.
authors.forename: Meiyan
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Gynecology and Obstetrics, Jilin University Bethune Second Hospital, Changchun, P. R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wu
authors.affiliation: Key Laboratory for Molecular and Chemical Genetics of Critical Human Diseases of Jilin Province, Jilin University Bethune Second Hospital, Changchun, P. R. China.
authors.forename: Longfei
authors.initials: L
authors.lastname: Yang
authors.affiliation: Key Laboratory for Molecular and Chemical Genetics of Critical Human Diseases of Jilin Province, Jilin University Bethune Second Hospital, Changchun, P. R. China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Di
authors.affiliation: Key Laboratory for Molecular and Chemical Genetics of Critical Human Diseases of Jilin Province, Jilin University Bethune Second Hospital, Changchun, P. R. China.
authors.forename: Guizhen
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Key Laboratory for Molecular and Chemical Genetics of Critical Human Diseases of Jilin Province, Jilin University Bethune Second Hospital, Changchun, P. R. China.
authors.forename: Lili
authors.initials: L
authors.lastname: Zhong
authors.affiliation: Department of General Surgery, Jilin University Bethune Second Hospital, Changchun, P. R. China.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Department of General Surgery, Jilin University Bethune Second Hospital, Changchun, P. R. China.
authors.forename: Jinhao
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of General Surgery, Jilin University Bethune Second Hospital, Changchun, P. R. China; Department of General Surgery, China-Japan Friendship Hospital of Jilin University, Changchun, P. R. China.
authors.forename: Xuedong
authors.initials: X
authors.lastname: Fang
authors.affiliation: Key Laboratory for Molecular and Chemical Genetics of Critical Human Diseases of Jilin Province, Jilin University Bethune Second Hospital, Changchun, P. R. China; College of Basic Medical Sciences, Dalian Medical University, Dalian, P. R. China.
authors.forename: Tonghui
authors.initials: T
authors.lastname: Ma
mesh_terms: D000075369:Anoctamin-1; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D045325:HCT116 Cells; D006801:Humans; D020935:MAP Kinase Signaling System; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism*
chemical_list: C476213:ANO1 protein, human; D000075369:Anoctamin-1; D018118:Chloride Channels; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering