Nuclear lamin A/C phosphorylation by loss of androgen receptor leads to cancer-associated fibroblast activation.
Details
Serval ID
serval:BIB_39467E97F3A5
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Nuclear lamin A/C phosphorylation by loss of androgen receptor leads to cancer-associated fibroblast activation.
Journal
Nature communications
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
12/09/2024
Peer-reviewed
Oui
Volume
15
Number
1
Pages
7984
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Publication Status: epublish
Abstract
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.
Keywords
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
Yes
Create date
17/09/2024 9:39
Last modification date
31/10/2024 7:13