title: TMEM16A overexpression contributes to tumor invasion and poor prognosis of human gastric cancer through TGF-β signaling.
abstract: TMEM16A is a newly identified calcium activated chloride channel, and has been reported to be overexpressed by various solid malignant cancers to promote proliferation and invasion, yet little is known about its role in gastric cancer(GC). Therefore, we investigated the role of TMEM16A in GC and its clinical significance by a retrospective analysis of 367 GC patients, and in vitro study was performed for validation and underlying molecular mechanism.TMEM16A was significantly upregulated and amplified in GC tissues, and its overexpression was positively correlated with disease stage, negatively with patient survival and identified as an independent prognostic factor for patient outcome. A negative correlation between TMEM16A and E-cadherin was found in 367 GC specimens. TMEM16A silencing significantly decreased calcium activated chloride currents, impaired TGF-β secretion, reduced E-cadherin expression, and inhibited the migration and invasion without affecting proliferation of GC cells (AGS and BGC-823). Supplement of TGF-β reverted the effects of TMEM16A silencing on E-cadherin expression, cell migration and invasion.In conclusion, TMEM16A promotes invasion and metastasis in GC, and might be a novel prognostic biomarker and potential therapeutic target in the treatment of GC.
authors.affiliation: Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.|Faculty of Forensic Medicine, ZhongShan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.|Cancer Center and Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou 510315, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Qing-Hua
authors.initials: QH
authors.lastname: Cao
authors.affiliation: Faculty of Forensic Medicine, ZhongShan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: De-Jian
authors.initials: DJ
authors.lastname: Lu
authors.affiliation: Faculty of Forensic Medicine, ZhongShan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Luo
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Lu
authors.affiliation: Cancer Center and Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou 510315, China.
authors.forename: Rong-Cheng
authors.initials: RC
authors.lastname: Luo
authors.affiliation: Faculty of Forensic Medicine, ZhongShan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Xiao-Guang
authors.initials: XG
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000075369:Anoctamin-1; D015703:Antigens, CD; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D034622:RNA Interference; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D013997:Time Factors; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C476213:ANO1 protein, human; D000075369:Anoctamin-1; D015703:Antigens, CD; D014408:Biomarkers, Tumor; C513384:CDH1 protein, human; D015820:Cadherins; D018118:Chloride Channels; D009363:Neoplasm Proteins; D016212:Transforming Growth Factor beta
keywords: TGF-β; TMEM16A; gastric cancer; invasion; prognosis
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