Targeting invadopodia to block breast cancer metastasis

Mark A. Eckert 1,2 and Jing Yang 1,3 1 Department of Pharmacology 2 The Molecular Pathology Graduate Program 3 Department of Pediatrics Received: June 30, 2011; Accepted: June 30, 2011; Published: June 30, 2011; Keywords: Twist1, PDGFR, Src, MMP, MT1-MMP, SFK, metastasis, invasion, breast cancer, invadopodia, podosomes Correspondence: Jing Yang, email: // // Abstract Better understanding the mechanisms underlying the metastatic process is essential to developing novel targeted therapeutics. Recently, invadopodia have been increasingly recognized as important drivers of local invasion in metastasis. Invadopodia are basally-localized, actin-rich structures that concentrate protease activity to areas of the cell in contact with the extracellular matrix. We recently found that the transcription factor Twist1, a central regulator of the epithelial-mesenchymal transition (EMT), promotes invadopodia formation via upregulation of platelet-derived growth factor receptor (PDGFR) expression and activity. This finding, combined with other investigations into the mechanisms of invadopodia formation, reveal several novel targets for clinical inhibition of invadopodia. Here, we provide an overview of clinically-relevant targets for intervention in invadopodia, including Src signaling, PDGFR signaling, and metalloprotease activity.