Carcinoma-associated fibroblast-derived lysyl oxidase-rich extracellular vesicles mediate collagen crosslinking and promote epithelial-mesenchymal transition via p-FAK/p-paxillin/YAP signaling / 国际口腔科学杂志·英文版
International Journal of Oral Science
; (4): 32-32, 2023.
Article
em En
| WPRIM
| ID: wpr-1010687
Biblioteca responsável:
WPRO
ABSTRACT
Carcinoma-associated fibroblasts (CAFs) are the main cellular components of the tumor microenvironment and promote cancer progression by modifying the extracellular matrix (ECM). The tumor-associated ECM is characterized by collagen crosslinking catalyzed by lysyl oxidase (LOX). Small extracellular vesicles (sEVs) mediate cell-cell communication. However, the interactions between sEVs and the ECM remain unclear. Here, we demonstrated that sEVs released from oral squamous cell carcinoma (OSCC)-derived CAFs induce collagen crosslinking, thereby promoting epithelial-mesenchymal transition (EMT). CAF sEVs preferably bound to the ECM rather than being taken up by fibroblasts and induced collagen crosslinking, and a LOX inhibitor or blocking antibody suppressed this effect. Active LOX (αLOX), but not the LOX precursor, was enriched in CAF sEVs and interacted with periostin, fibronectin, and bone morphogenetic protein-1 on the surface of sEVs. CAF sEV-associated integrin α2β1 mediated the binding of CAF sEVs to collagen I, and blocking integrin α2β1 inhibited collagen crosslinking by interfering with CAF sEV binding to collagen I. CAF sEV-induced collagen crosslinking promoted the EMT of OSCC through FAK/paxillin/YAP pathway. Taken together, these findings reveal a novel role of CAF sEVs in tumor ECM remodeling, suggesting a critical mechanism for CAF-induced EMT of cancer cells.
Texto completo:
1
Base de dados:
WPRIM
Assunto principal:
Neoplasias Bucais
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Carcinoma de Células Escamosas
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Colágeno
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Integrina alfa2beta1
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Linhagem Celular Tumoral
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Paxilina
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Transição Epitelial-Mesenquimal
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Microambiente Tumoral
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Fibroblastos
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Vesículas Extracelulares
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article