2026-06-14T03:40:42Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/132102024-10-31T12:01:49Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Albacete-Albacete, Lucas author Navarro-Lerida, Inmaculada author Lopez, Juan Antonio author Martin-Padura, Ines author Astudillo, Alma M author Ferrarini, Alessia author Van-Der-Heyden, Michael author Balsinde, Jesus author Orend, Gertraud author Vazquez, Jesus author del Pozo, Miguel Angel author 2020-11 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. J Cell Biol. 2020; 219(11):e202006178 10.1083/jcb.202006178 1540-8140 The Journal of cell biology 33053168 http://hdl.handle.net/20.500.12105/13210 ECM deposition is driven by caveolin-1-dependent regulation of exosomal biogenesis and cargo sorting.