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Cancer Cell. 2011 Mar 8;19(3):372-86. doi: 10.1016/j.ccr.2011.01.036.

Twist1-induced invadopodia formation promotes tumor metastasis.

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  • 1Department of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0636, USA.

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.

Copyright © 2011 Elsevier Inc. All rights reserved.

PMID:
21397860
[PubMed - indexed for MEDLINE]
PMCID:
PMC3072410
Free PMC Article

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