ECM deposition is driven by caveolin-1-dependent regulation of exosomal biogenesis and cargo sorting.

Autor:	Albacete-Albacete L; Mechanoadaptation and Caveolae Biology Laboratory, Cell and Developmental Biology Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain., Navarro-Lérida I; Mechanoadaptation and Caveolae Biology Laboratory, Cell and Developmental Biology Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain., López JA; Cardiovascular Proteomics Lab, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, Madrid, Spain., Martín-Padura I; Mechanoadaptation and Caveolae Biology Laboratory, Cell and Developmental Biology Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain., Astudillo AM; Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas, Universidad de Valladolid, Valladolid, Spain.; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas, Instituto de Salud Carlos III, Madrid, Spain., Ferrarini A; Cardiovascular Proteomics Lab, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain., Van-Der-Heyden M; Institut National de la Santé et de la Recherche Médicale U1109-MN3T, The Microenvironmental Niche in Tumorigenesis and Targeted Therapy, Université de Strasbourg, LabEx Medalis, Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France., Balsinde J; Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas, Universidad de Valladolid, Valladolid, Spain.; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas, Instituto de Salud Carlos III, Madrid, Spain., Orend G; Institut National de la Santé et de la Recherche Médicale U1109-MN3T, The Microenvironmental Niche in Tumorigenesis and Targeted Therapy, Université de Strasbourg, LabEx Medalis, Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France., Vázquez J; Cardiovascular Proteomics Lab, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, Madrid, Spain., Del Pozo MÁ; Mechanoadaptation and Caveolae Biology Laboratory, Cell and Developmental Biology Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain.
Jazyk:	angličtina
Zdroj:	The Journal of cell biology [J Cell Biol] 2020 Nov 02; Vol. 219 (11).
DOI:	10.1083/jcb.202006178
Abstrakt:	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. (© 2020 Albacete-Albacete et al.)
Databáze:	MEDLINE
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