| Literature DB >> 27779657 |
Min Xu1, Hailang Zhou1, Chunli Zhang1, Junbo He1, Hong Wei1, Meng Zhou1, Ying Lu1, Yaocheng Sun1, Jerry Wanming Ding2, Jian Zeng3, Wanxin Peng3, Fengyi Du3, Aihua Gong3.
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.Entities:
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Year: 2016 PMID： 27779657 DOI： 10.3892/ijo.2016.3744
Source DB: PubMed Journal: Int J Oncol ISSN： 1019-6439 Impact factor: 5.650