Cancer Cell
Volume 19, Issue 3, 8 March 2011, Pages 372-386
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Article
Twist1-Induced Invadopodia Formation Promotes Tumor Metastasis

https://doi.org/10.1016/j.ccr.2011.01.036Get rights and content
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Summary

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.

Highlights

► Twist1 promotes invadopodia-mediated extracellular matrix degradation ► Twist1 induces PDGFRα and activates Src to promote invadopodia formation ► Induction of PDGFRα and invadopodia is required for Twist1 to promote metastasis ► Coexpression of Twist1 and PDGFRα predicts poor survival in breast tumor patients

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