ECM deposition is driven by caveolin-1-dependent regulation of exosomal biogenesis and cargo sorting.
J Cell Biol
; 219(11)2020 11 02.
Article
en En
| MEDLINE
| ID: mdl-33053168
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Tenascina
/
Proteoma
/
Caveolina 1
/
Matriz Extracelular
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Exosomas
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Cuerpos Multivesiculares
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Fibroblastos
Límite:
Animals
Idioma:
En
Revista:
J Cell Biol
Año:
2020
Tipo del documento:
Article
País de afiliación:
España