title: ADAM17 promotes epithelial-mesenchymal transition via TGF-β/Smad pathway in gastric carcinoma cells.
abstract: Although a disintegrin and metalloproteinase-17 (ADAM17) overexpression has been demonstrated in numerous human tumors including gastric cancer, its role in gastric cancer development remains to be clarified. In the present study, we identify that ADAM17 activates TGF-β/Smad signaling to promote epithelial-mesenchymal transition (EMT) in gastric cancer cells. We found that ADAM17 promotes proliferation, migration and invasion in gastric carcinoma cells. Subsequently, we revealed that silencing ADAM17 induces the expression of epithelial marker of E-cadherin and downregulates expression of mesenchymal markers including N-cadherin, vimentin and Snail in MGC803 and MKN45 cells, whereas ADAM17 overexpression reverses these changes in BGC823 and HGC27 cells. Furthermore, ADAM17 knockdown significantly inhibits the expression of TGF-β and its downstream signaling molecules p-Smad2 and p-Smad3 in MGC803 and MKN45 cells. Consistently, ADAM17 overexpression reversed these changes in BGC823 and HGC27 cells. These results suggest that ADAM17 promotes epithelial-mesenchymal transition via the TGF-β/Smad pathway. Collectively, the present study demonstrates that ADAM17 plays a critical role in the development of gastric cancer and provides a potential therapeutic target for gastric cancer.
authors: Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, Jiangsu, P.R. China.
authors: Min
authors: M
authors: Xu
authors: Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, Jiangsu, P.R. China.
authors: Hailang
authors: H
authors: Zhou
authors: Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, Jiangsu, P.R. China.
authors: Chunli
authors: C
authors: Zhang
authors: Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, Jiangsu, P.R. China.
authors: Junbo
authors: J
authors: He
authors: Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, Jiangsu, P.R. China.
authors: Hong
authors: H
authors: Wei
authors: Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, Jiangsu, P.R. China.
authors: Meng
authors: M
authors: Zhou
authors: Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, Jiangsu, P.R. China.
authors: Ying
authors: Y
authors: Lu
authors: Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, Jiangsu, P.R. China.
authors: Yaocheng
authors: Y
authors: Sun
authors: Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON, N6A 5C1, Canada.
authors: Jerry Wanming
authors: JW
authors: Ding
authors: Department of Cell Biology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, P.R. China.
authors: Jian
authors: J
authors: Zeng
authors: Department of Cell Biology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, P.R. China.
authors: Wanxin
authors: W
authors: Peng
authors: Department of Cell Biology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, P.R. China.
authors: Fengyi
authors: F
authors: Du
authors: Department of Cell Biology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, P.R. China.
authors: Aihua
authors: A
authors: Gong
mesh_terms: D000072198:ADAM17 Protein / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D006801:Humans; D009361:Neoplasm Invasiveness / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D051899:Smad2 Protein / Q000378:metabolism*; D051900:Smad3 Protein / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human