Twist1 诱导的侵袭伪足形成促进肿瘤转移。
Twist1-induced invadopodia formation promotes tumor metastasis.
机构信息
Department of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0636, USA.
出版信息
Cancer Cell. 2011 Mar 8;19(3):372-86. doi: 10.1016/j.ccr.2011.01.036.
Abstract
The Twist1 transcription factor is known to promote tumor metastasis and induce Epithelial-Mesenchymal Transition (EMT). Here, we report that Twist1 is capable of promoting the formation of invadopodia, specialized membrane protrusions for extracellular matrix degradation. Twist1 induces PDGFRα expression, which in turn activates Src, to promote invadopodia formation. We show that Twist1 and PDGFRα are central mediators of invadopodia formation in response to various EMT-inducing signals. Induction of PDGFRα and invadopodia is essential for Twist1 to promote tumor metastasis. Consistent with PDGFRα being a direct transcriptional target of Twist1, coexpression of Twist1 and PDGFRα predicts poor survival in breast tumor patients. Therefore, invadopodia-mediated matrix degradation is a key function of Twist1 in promoting tumor metastasis.
摘要
扭转型蛋白 1（Twist1）转录因子已知可促进肿瘤转移并诱导上皮-间充质转化（EMT）。在这里，我们报告 Twist1 能够促进侵袭伪足的形成，侵袭伪足是细胞外基质降解的特殊膜突起。Twist1 诱导血小板衍生生长因子受体α（PDGFRα）的表达，而 PDGFRα 又反过来激活Src，从而促进侵袭伪足的形成。我们表明，Twist1 和 PDGFRα 是响应各种 EMT 诱导信号形成侵袭伪足的中心介质。PDGFRα 和侵袭伪足的诱导对于 Twist1 促进肿瘤转移是必不可少的。与 PDGFRα 是 Twist1 的直接转录靶标一致，Twist1 和 PDGFRα 的共表达预测乳腺癌患者的预后不良。因此，侵袭伪足介导的基质降解是 Twist1 促进肿瘤转移的关键功能。
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