Nuclear lamin A/C phosphorylation by loss of androgen receptor leads to cancer-associated fibroblast activation.
Détails
ID Serval
serval:BIB_39467E97F3A5
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Nuclear lamin A/C phosphorylation by loss of androgen receptor leads to cancer-associated fibroblast activation.
Périodique
Nature communications
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Statut éditorial
Publié
Date de publication
12/09/2024
Peer-reviewed
Oui
Volume
15
Numéro
1
Pages
7984
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Publication Status: epublish
Résumé
Alterations in nuclear structure and function are hallmarks of cancer cells. Little is known about these changes in Cancer-Associated Fibroblasts (CAFs), crucial components of the tumor microenvironment. Loss of the androgen receptor (AR) in human dermal fibroblasts (HDFs), which triggers early steps of CAF activation, leads to nuclear membrane changes and micronuclei formation, independent of cellular senescence. Similar changes occur in established CAFs and are reversed by restoring AR activity. AR associates with nuclear lamin A/C, and its loss causes lamin A/C nucleoplasmic redistribution. AR serves as a bridge between lamin A/C and the protein phosphatase PPP1. Loss of AR decreases lamin-PPP1 association and increases lamin A/C phosphorylation at Ser 301, a characteristic of CAFs. Phosphorylated lamin A/C at Ser 301 binds to the regulatory region of CAF effector genes of the myofibroblast subtype. Expression of a lamin A/C Ser301 phosphomimetic mutant alone can transform normal fibroblasts into tumor-promoting CAFs.
Mots-clé
Humans, Receptors, Androgen/metabolism, Receptors, Androgen/genetics, Lamin Type A/metabolism, Lamin Type A/genetics, Phosphorylation, Cancer-Associated Fibroblasts/metabolism, Cancer-Associated Fibroblasts/pathology, Cell Nucleus/metabolism, Protein Phosphatase 1/metabolism, Protein Phosphatase 1/genetics, Fibroblasts/metabolism, Nuclear Envelope/metabolism, Male, Tumor Microenvironment
Pubmed
Web of science
Open Access
Oui
Création de la notice
17/09/2024 9:39
Dernière modification de la notice
31/10/2024 7:13