Nuclear lamin A/C phosphorylation by loss of Androgen Receptor is a global determinant of cancer-associated fibroblast activation.

ABSTRACT: Alterations of nuclear structure and function, and associated impact on gene transcription, are a hallmark of cancer cells. Little is known of these alterations in Cancer-Associated Fibroblasts (CAFs), a key component of the tumor stroma. Here we show that loss of androgen receptor (AR), which triggers early steps of CAF activation in human dermal fibroblasts (HDFs), leads to nuclear membrane alterations and increased micronuclei formation, which are unlinked from induction of cellular senescence. Similar alterations occur in fully established CAFs, which are overcome by restored AR function. AR associates with nuclear lamin A/C and loss of AR results in a substantially increased lamin A/C nucleoplasmic redistribution. Mechanistically, AR functions as a bridge between lamin A/C with the pr

SUBMITTER: Ghosh S 

PROVIDER: S-EPMC10327063 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature