期刊
CELL CYCLE
卷 12, 期 21, 页码 3377-3389出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.26388
关键词
TGF-beta; adhesion; epithelial-mesenchymal transition; integrin; ventral stress fibers; zyxin
类别
资金
- NYSDOH-HSRB Peter T Rowley Breast Cancer Project
- Roswell Park Cancer Institute Cancer Center Support Grant [CA 16056]
Cell adhesion to the extracellular matrix is an essential element of various biological processes. TGF- cytokines regulate the matrix components and cell-matrix adhesions. The present study investigates the molecular organization of TGF-beta-induced matrix adhesions. The study demonstrates that in various mouse and human epithelial cells TGF-beta induces cellular structures containing 2 matrix adhesions bridged by a stretch of actin fibers. These structures are similar to ventral stress fibers (VSFs). Suppression of integrin-beta 5 by RNA interference reduces VSFs in majority of cells (>75%), while overexpression of integrin-beta 5 fragments revealed a critical role of a distinct sequence in the cytoplasmic domain of integrin-beta 5 in the VSF structures. In addition, the integrity of actin fibers and Src kinase activity contribute to integrin-beta 5-mediated signaling and VSF formation. TGF-beta-Smad signaling upregulates actin-regulatory proteins, such as caldesmon, zyxin, and zyxin-binding protein Csrp1 in mouse and human epithelial cells. Suppression of zyxin markedly inhibits formation of VSFs in response to TGF-beta and integrin-beta 5. Zyxin is localized at actin fibers and matrix adhesions of VSFs and might bridge integrin-beta 5-mediated adhesions to actin fibers. These findings provide a platform for defining the molecular mechanism regulating the organization and activities of VSFs in response to TGF-beta.
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