Carcinoma-associated fibroblast-derived lysyl oxidase-rich extracellular vesicles mediate collagen crosslinking and promote epithelial-mesenchymal transition via p-FAK/p-paxillin/YAP signaling.
Humans
Paxillin
/ metabolism
Protein-Lysine 6-Oxidase
/ metabolism
Carcinoma, Squamous Cell
/ pathology
Epithelial-Mesenchymal Transition
Integrin alpha2beta1
/ metabolism
Mouth Neoplasms
/ pathology
Collagen
/ metabolism
Fibroblasts
Extracellular Vesicles
/ metabolism
Cell Line, Tumor
Tumor Microenvironment
Journal
International journal of oral science
ISSN: 2049-3169
Titre abrégé: Int J Oral Sci
Pays: India
ID NLM: 101504351
Informations de publication
Date de publication:
02 08 2023
02 08 2023
Historique:
received:
11
01
2023
accepted:
05
07
2023
revised:
05
07
2023
medline:
4
8
2023
pubmed:
3
8
2023
entrez:
2
8
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 37532712
doi: 10.1038/s41368-023-00236-1
pii: 10.1038/s41368-023-00236-1
pmc: PMC10397209
doi:
Substances chimiques
Paxillin
0
Protein-Lysine 6-Oxidase
EC 1.4.3.13
Integrin alpha2beta1
0
Collagen
9007-34-5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
32Informations de copyright
© 2023. The Author(s).
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