Role of β5-integrin in epithelial-mesenchymal transition in response to TGFβ

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.