Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY, USA.
Cell Cycle. 2010 Apr 15;9(8):1647-59. 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.
上皮-间充质转化（EMT）对 TGFβ 的反应有助于正常发育、伤口愈合和肿瘤进展。本研究为β5-整联蛋白在 TGFβ 诱导的 EMT 和癌细胞的致瘤潜能中的关键作用提供了证据。我们表明，在 TGFβ 诱导的 EMT 过程中，αvβ-整联蛋白亚基上调，这种反应需要 Smad 转录因子。siRNA 耗竭αv-整联蛋白可阻断 EMT 反应，而β1-整联蛋白的敲低则没有影响。重要的是，β5-整联蛋白的耗竭阻断了 TGFβ 诱导的 EMT，损害了细胞-基质附着和整联蛋白信号传导，但不改变 E-钙粘蛋白和 TGFβ 靶基因的表达。因此，cRGD 肽干扰细胞-基质附着或抑制粘着斑激酶可阻断 EMT 过程和整合素信号传导，表明β5-整联蛋白介导的黏附在 EMT 中的重要性。最后，β5-整联蛋白的耗竭显著降低了乳腺癌细胞的侵袭性。因此，β5-整联蛋白黏附有助于 TGFβ 诱导的 EMT 和癌细胞的致瘤潜能。
