Journal
CELL CYCLE
Volume 9, Issue 8, Pages 1647-1659Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.9.8.11517
Keywords
epithelial-mesenchymal transition; integrin; focal adhesion; actin fibers; TGF beta; invasion
Categories
Funding
- PHS [R01 CA95263]
- Roswell Park Cancer Institute Cancer Center [CA 16056]
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Epithelial-mesenchymal-transition (EMT) in response to TGF beta contributes to normal development, wound healing and tumor progression. The present study provides evidence for a critical role of beta 5-integrin in the TGF beta-induced EMT and the tumorigenic potential of carcinoma cells. We show that the alpha v beta-integrin subunits are upregulated during the TGF beta-induced EMT and this response requires Smad transcription factors. Depletion of alpha v-integrin by siRNA blocked the EMT response whereas knock-down of beta 1-integrin had no effect. Importantly, depletion of beta 5-integrin blocked the TGF beta-induced EMT impairing adhesion to cell-matrix and integrin signaling, but did not change expression of E-cadherin and TGF beta-target genes. Accordingly, the EMT process and integrin signaling were blocked by cRGD peptide interfering with cell-matrix adhesion or by inhibition of focal adhesion kinase, indicating the importance of beta 5-integrin-mediated adhesions in EMT. Finally, depletion of beta 5-integrin significantly reduced invasiveness of breast carcinoma cells. Thus, the beta 5-integrin adhesions contribute to the TGF beta-induced EMT and the tumorigenic potential of carcinoma cells.
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