Twist1-Induced Invadopodia Formation Promotes Tumor Metastasis

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