title: Targeting invadopodia to block breast cancer metastasis.
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.
authors: Department of Pharmacology.
authors: Mark A
authors: MA
authors: Eckert
authors: Jing
authors: J
authors: Yang
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D022081:Cell Surface Extensions / Q000187:drug effects* / Q000648:ultrastructure; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006801:Humans; D045726:Metalloproteases / Q000378:metabolism; D051379:Mice; D058990:Molecular Targeted Therapy; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000517:prevention & control; D009687:Nuclear Proteins / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000096:biosynthesis / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D051879:Twist-Related Protein 1 / Q000378:metabolism*; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000199:Actins; D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; D017479:Receptors, Platelet-Derived Growth Factor; D019061:src-Family Kinases; D045726:Metalloproteases; D010447:Peptide Hydrolases