Journal
INTERNATIONAL JOURNAL OF ONCOLOGY
Volume 49, Issue 6, Pages 2520-2528Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/ijo.2016.3744
Keywords
ADAM17; epithelial-mesenchymal transition; gastric carcinoma cells; migration and invasion; TGF-beta/Smad signaling
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Funding
- National Natural Science Foundation of China [81472333, 81372718]
- Natural Science Foundation of Jiangsu Province [BK20131247]
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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-beta/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-beta 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-beta/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.
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