| First Author | Albacete-Albacete L | Year | 2020 |
| Journal | J Cell Biol | Volume | 219 |
| Issue | 11 | PubMed ID | 33053168 |
| Mgi Jnum | J:305489 | Mgi Id | MGI:6705818 |
| Doi | 10.1083/jcb.202006178 | Citation | Albacete-Albacete L, et al. (2020) ECM deposition is driven by caveolin-1-dependent regulation of exosomal biogenesis and cargo sorting. J Cell Biol 219(11) |
| abstractText | The composition and physical properties of the extracellular matrix (ECM) critically influence tumor progression, but the molecular mechanisms underlying ECM layering are poorly understood. Tumor-stroma interaction critically depends on cell communication mediated by exosomes, small vesicles generated within multivesicular bodies (MVBs). We show that caveolin-1 (Cav1) centrally regulates exosome biogenesis and exosomal protein cargo sorting through the control of cholesterol content at the endosomal compartment/MVBs. Quantitative proteomics profiling revealed that Cav1 is required for exosomal sorting of ECM protein cargo subsets, including Tenascin-C (TnC), and for fibroblast-derived exosomes to efficiently deposit ECM and promote tumor invasion. Cav1-driven exosomal ECM deposition not only promotes local stromal remodeling but also the generation of distant ECM-enriched stromal niches in vivo. Cav1 acts as a cholesterol rheostat in MVBs, determining sorting of ECM components into specific exosome pools and thus ECM deposition. This supports a model by which Cav1 is a central regulatory hub for tumor-stroma interactions through a novel exosome-dependent ECM deposition mechanism. |
