Role of β5-integrin in epithelial-mesenchymal transition in response to TGF-β

• Published in: Cell cycle (Georgetown, Tex.) Tex.), 2010-04, Vol.9 (8), p.1647-1659
• Main Authors: Bianchi, Anna, Gervasi, Megan E., Bakin, Andrei
• Format: Article
• Language: English
• Subjects: Animals; Binding; Biology; Bioscience; Cadherins - metabolism; Calcium; Cancer; Cell; Cell Line; Cycle; Epithelial-Mesenchymal Transition; Humans; Integrin alpha5 - chemistry; Integrin alpha5 - genetics; Integrin alpha5 - metabolism; Integrin beta Chains - genetics; Integrin beta Chains - metabolism; Integrin beta Chains - physiology; Landes; Mice; Organogenesis; Proteins; RNA Interference; RNA, Small Interfering - metabolism; Signal Transduction; Smad3 Protein - antagonists & inhibitors; Smad3 Protein - genetics; Smad3 Protein - metabolism; Smad4 Protein - antagonists & inhibitors; Smad4 Protein - genetics; Smad4 Protein - metabolism; Transforming Growth Factor beta - metabolism
• ISSN: 1538-4101; 1551-4005
• DOI: 10.4161/cc.9.8.11517

Epithelial-mesenchymal-transition (EMT) in response to TGFβ contributes to normal development, wound healing and tumor progression. The present study provides evidence for a critical role of β5-integrin in the TGFβ-induced EMT and the tumorigenic potential of carcinoma cells. We show that the αvβ-integrin subunits are upregulated during the TGFβ-induced EMT and this response requires Smad transcription factors. Depletion of αv-integrin by siRNA blocked the EMT response whereas knock-down of β1-integrin had no effect. Importantly, depletion of β5-integrin blocked the TGFβ-induced EMT impairing adhesion to cell-matrix and integrin signaling, but did not change expression of E-cadherin and TGFβ-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 β5-integrin-mediated adhesions in EMT. Finally, depletion of β5-integrin significantly reduced invasiveness of breast carcinoma cells. Thus, the β5-integrin adhesions contribute to the TGFβ-induced EMT and the tumorigenic potential of carcinoma cells.