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Stiff substrates increase YAP-signaling-mediated matrix metalloproteinase-7 expression


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タイトル: Stiff substrates increase YAP-signaling-mediated matrix metalloproteinase-7 expression
著者: Nukuda, A. 著作を一覧する
Sasaki, C. 著作を一覧する
Ishihara, S. 著作を一覧する
Mizutani, T. 著作を一覧する
Nakamura, K. 著作を一覧する
Ayabe, T. 著作を一覧する
Kawabata, K. 著作を一覧する
Haga, H. 著作を一覧する
発行日: 2015年 9月 7日
出版者: Nature Publishing Group
誌名: Oncogenesis
巻: 4
開始ページ: e165
出版社 DOI: 10.1038/oncsis.2015.24
抄録: Abnormally stiff substrates have been shown to trigger cancer progression. However, the detailed molecular mechanisms underlying this trigger are not clear. In this study, we cultured T84 human colorectal cancer cells on plastic dishes to create a stiff substrate or on collagen-I gel to create a soft substrate. The stiff substrate enhanced the expression of matrix metalloproteinase-7 (MMP-7), an indicator of poor prognosis. In addition, we used polyacrylamide gels (2, 67 and 126 kPa) so that the MMP-7 expression on the 126-kPa gel was higher compared with that on the 2-kPa gel. Next, we investigated whether yes-associated protein (YAP) affected the MMP-7 expression. YAP knockdown decreased MMP-7 expression. Treatment with inhibitors of epidermal growth factor receptor (EGFR) and myosin regulatory light chain (MRLC) and integrin-alpha 2 or integrin-beta 1 knockdown downregulated MMP-7 expression. Finally, we demonstrated that YAP, EGFR, integrin-alpha 2 beta 1 and MRLC produced a positive feedback loop that enhanced MMP-7 expression. These findings suggest that stiff substrates enhanced colorectal cancer cell viability by upregulating MMP-7 expression through a positive feedback loop.
資料タイプ: article
出現コレクション:雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

提供者: 芳賀 永


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