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-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.
Bianchi
Anna
A
Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY, USA.
Gervasi
Megan E
ME
Bakin
Andrei
A
D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002460:Cell Line; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D039482:Integrin alpha5 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D039641:Integrin beta Chains / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D051900:Smad3 Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051901:Smad4 Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D015820:Cadherins; D039482:Integrin alpha5; D039641:Integrin beta Chains; D034741:RNA, Small Interfering; D051900:Smad3 Protein; D051901:Smad4 Protein; D016212:Transforming Growth Factor beta; C084344:integrin beta5