Twist1-induced invadopodia formation promotes tumor metastasis.

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 PDGFR? expression, which in turn activates Src, to promote invadopodia formation. We show that Twist1 and PDGFR? are central mediators of invadopodia formation in response to various EMT-inducing signals. Induction of PDGFR? and invadopodia is essential for Twist1 to promote tumor metastasis. Consistent with PDGFR? being a direct transcriptional target of Twist1, coexpression of Twist1 and PDGFR? predicts poor survival in breast tumor patients. Therefore, invadopodia-mediated matrix degradation is a key function of Twist1 in promoting tumor metastasis.

SUBMITTER: Eckert MA 

PROVIDER: S-EPMC3072410 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature