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

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Title: Stiff substrates increase YAP-signaling-mediated matrix metalloproteinase-7 expression
Authors: Nukuda, A. Browse this author
Sasaki, C. Browse this author
Ishihara, S. Browse this author
Mizutani, T. Browse this author
Nakamura, K. Browse this author
Ayabe, T. Browse this author
Kawabata, K. Browse this author
Haga, H. Browse this author →KAKEN DB
Issue Date: 7-Sep-2015
Publisher: Nature Publishing Group
Journal Title: Oncogenesis
Volume: 4
Start Page: e165
Publisher DOI: 10.1038/oncsis.2015.24
PMID: 26344692
Abstract: 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.
Type: article
Appears in Collections:生命科学院・先端生命科学研究院 (Graduate School of Life Science / Faculty of Advanced Life Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 芳賀 永

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