Laboratorio de Biología Celular, Instituto de Nutrición y Tecnología de los Alimentos, Universidad de Chile, Santiago, Chile.
FEBS Lett. 2010 Nov 19;584(22):4586-92. doi: 10.1016/j.febslet.2010.10.020. Epub 2010 Oct 19.
Transforming growth factor-β1 (TGF-β1) potently induces the epithelial-mesenchymal transition (EMT) during tumoral progression. Although Sky-interacting protein (SKIP) regulates TGF-β1-induced Smad activation, its role in the induction of cell malignance remains uncertain. We found that TGF-β1 increases SKIP expression in PDV cells. In cells stably transfected with SKIP antisense, AS-S, Smad3 activation decreased, along with an inhibition of TGF-β1-induced EMT, and the cells were sensitized to the TGF-β1-dependent inhibition of proliferation. Also, AS-S cells showed a weaker migration and invasion response. Moreover, TGF-β1-induced urokinase-type plasminogen activator expression was inhibited, concomitantly with a TGF-β1-independent increment of the plasminogen-activator inhibitor-1 expression. Thus, these results suggest that SKIP is required for EMT and invasiveness induced by TGF-β1 in transformed cells.
转化生长因子-β1（TGF-β1）在肿瘤进展过程中能强有力地诱导上皮-间充质转化（EMT）。尽管 Sky 相互作用蛋白（SKIP）调节 TGF-β1 诱导的 Smad 激活，但它在诱导细胞恶性转化中的作用仍不确定。我们发现 TGF-β1 增加了 PDV 细胞中 SKIP 的表达。在稳定转染 SKIP 反义的细胞中，AS-S，Smad3 激活减少，同时抑制了 TGF-β1 诱导的 EMT，细胞对 TGF-β1 依赖性增殖抑制变得敏感。此外，AS-S 细胞的迁移和侵袭反应较弱。此外，TGF-β1 诱导的尿激酶型纤溶酶原激活物的表达受到抑制，同时 TGF-β1 非依赖性的纤溶酶原激活物抑制剂-1 的表达增加。因此，这些结果表明 SKIP 是 TGF-β1 在转化细胞中诱导 EMT 和侵袭所必需的。
