Extracellular vesicles in fatty liver promote a metastatic tumor microenvironment.
CYR61
M2 macrophage
Rab27a
colon cancer
exosome
high-fat diet
liver metastasis
microRNA
non-alcoholic fatty liver disease
palmitate
Journal
Cell metabolism
ISSN: 1932-7420
Titre abrégé: Cell Metab
Pays: United States
ID NLM: 101233170
Informations de publication
Date de publication:
11 07 2023
11 07 2023
Historique:
received:
31
05
2022
revised:
20
02
2023
accepted:
13
04
2023
pmc-release:
11
07
2024
medline:
14
7
2023
pubmed:
13
5
2023
entrez:
12
5
2023
Statut:
ppublish
Résumé
Liver metastasis is a major cause of death in patients with colorectal cancer (CRC). Fatty liver promotes liver metastasis, but the underlying mechanism remains unclear. We demonstrated that hepatocyte-derived extracellular vesicles (EVs) in fatty liver enhanced the progression of CRC liver metastasis by promoting oncogenic Yes-associated protein (YAP) signaling and an immunosuppressive microenvironment. Fatty liver upregulated Rab27a expression, which facilitated EV production from hepatocytes. In the liver, these EVs transferred YAP signaling-regulating microRNAs to cancer cells to augment YAP activity by suppressing LATS2. Increased YAP activity in CRC liver metastasis with fatty liver promoted cancer cell growth and an immunosuppressive microenvironment by M2 macrophage infiltration through CYR61 production. Patients with CRC liver metastasis and fatty liver had elevated nuclear YAP expression, CYR61 expression, and M2 macrophage infiltration. Our data indicate that fatty liver-induced EV-microRNAs, YAP signaling, and an immunosuppressive microenvironment promote the growth of CRC liver metastasis.
Identifiants
pubmed: 37172577
pii: S1550-4131(23)00140-7
doi: 10.1016/j.cmet.2023.04.013
pmc: PMC10524732
mid: NIHMS1897984
pii:
doi:
Substances chimiques
MicroRNAs
0
LATS2 protein, human
EC 2.7.1.11
Protein Serine-Threonine Kinases
EC 2.7.11.1
Tumor Suppressor Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1209-1226.e13Subventions
Organisme : NCI NIH HHS
ID : P01 CA233452
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK085252
Pays : United States
Organisme : NIAAA NIH HHS
ID : R21 AA025841
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2023 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests M.N. is a member of the advisory board of Altimmune, BI, BMS, Cytodyn, 89BIO, EchoSens, Gilead, GSK, Madrgial, Merck, Novo Nordisk, OWL, Prespecturm, Pfizer, Roche Diagnostic, and Siemens, Terns and Takeda; received research support from Allergan, Akero, BMS, Gilead, Galectin, Genfit, GSK, Conatus, Corcept, Enanta, Madrigal, Novartis, Novo Nordisk, Shire, Takeda, Terns, Viking, and Zydus; and is a stockholder in Anaetos, Rivus Pharma, CIMA, ChronWell, and Viking.
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