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

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-in...

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Bibliographic Details
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
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Summary: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.
ISSN:1538-4101
1551-4005
DOI:10.4161/cc.9.8.11517