2026-06-14T03:36:04Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/132102024-10-31T12:01:49Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
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
funder
Ministerio de Ciencia, Innovación y Universidades (España)
funder
Fundación La Marató TV3
funder
Worldwide Cancer Research
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Unión Europea. Comisión Europea. H2020
funder
Institut National de la Santé et de la Recherche Médicale (Francia)
funder
University of Strasbourg (Francia)
funder
Ligue Nationale Contre le Cancer (Francia)
funder
French National Cancer Institute
funder
Asociación Española Contra el Cáncer
funder
Ministerio de Ciencia e Innovación (España)
funder
Fundación ProCNIC
2021-06-29T09:07:04Z
2021-06-29T09:07:04Z
2020-11
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
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.
eng
ECM deposition is driven by caveolin-1-dependent regulation of exosomal biogenesis and cargo sorting.
journal article
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