Endothelial Notch1 signaling in white adipose tissue promotes cancer cachexia.
Journal
Nature cancer
ISSN: 2662-1347
Titre abrégé: Nat Cancer
Pays: England
ID NLM: 101761119
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
received:
11
04
2023
accepted:
20
07
2023
medline:
23
11
2023
pubmed:
26
9
2023
entrez:
25
9
2023
Statut:
ppublish
Résumé
Cachexia is a major cause of morbidity and mortality in individuals with cancer and is characterized by weight loss due to adipose and muscle tissue wasting. Hallmarks of white adipose tissue (WAT) remodeling, which often precedes weight loss, are impaired lipid storage, inflammation and eventually fibrosis. Tissue wasting occurs in response to tumor-secreted factors. Considering that the continuous endothelium in WAT is the first line of contact with circulating factors, we postulated whether the endothelium itself may orchestrate tissue remodeling. Here, we show using human and mouse cancer models that during precachexia, tumors overactivate Notch1 signaling in distant WAT endothelium. Sustained endothelial Notch1 signaling induces a WAT wasting phenotype in male mice through excessive retinoic acid production. Pharmacological blockade of retinoic acid signaling was sufficient to inhibit WAT wasting in a mouse cancer cachexia model. This demonstrates that cancer manipulates the endothelium at distant sites to mediate WAT wasting by altering angiocrine signals.
Identifiants
pubmed: 37749321
doi: 10.1038/s43018-023-00622-y
pii: 10.1038/s43018-023-00622-y
pmc: PMC10663158
doi:
Substances chimiques
Tretinoin
5688UTC01R
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1544-1560Subventions
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : 394046768 - SFB1366
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : SFB1118-A04/S01
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : BO 1639/9-1
Informations de copyright
© 2023. The Author(s).
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