title: Invasive matrix degradation at focal adhesions occurs via protease recruitment by a FAK-p130Cas complex.
abstract: Tumor cell migration and the concomitant degradation of extracellular matrix (ECM) are two essential steps in the metastatic process. It is well established that focal adhesions (FAs) play an important role in regulating migration; however, whether these structures contribute to matrix degradation is not clear. In this study, we report that multiple cancer cell lines display degradation of ECM at FA sites that requires the targeted action of MT1-MMP. Importantly, we have found that this MT1-MMP targeting is dependent on an association with a FAK-p130Cas complex situated at FAs and is regulated by Src-mediated phosphorylation of Tyr 573 at the cytoplasmic tail of MT1. Disrupting the FAK-p130Cas-MT1 complex significantly impairs FA-mediated degradation and tumor cell invasion yet does not appear to affect invadopodia formation or function. These findings demonstrate a novel function for FAs and also provide molecular insights into MT1-MMP targeting and function.
authors.affiliation: Department of Biochemistry and Molecular Biology, and the Center for Basic Research in Digestive Diseases, Mayo Clinic and Graduate School, Rochester, MN 55905, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Mark A
authors.initials: MA
authors.lastname: McNiven
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D050719:Crk-Associated Substrate Protein / Q000235:genetics / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism*; D022001:Focal Adhesions / Q000378:metabolism*; D006801:Humans; D008856:Microscopy, Fluorescence; D009361:Neoplasm Invasiveness; D051381:Rats
chemical_list: D050719:Crk-Associated Substrate Protein; D051417:Focal Adhesion Kinase 1; C496052:Ptk2 protein, rat