Intra-epithelial non-canonical Activin A signalling safeguards prostate progenitor quiescence

ABSTRACT: The healthy prostate is a relatively quiescent tissue. Yet, prostate epithelium overgrowth is a common condition during ageing, associated with urinary dysfunction and tumorigenesis. For over thirty years, TGF-β ligands have been known to induce cytostasis in a variety of epithelia, but the intracellular pathway mediating this signal in the prostate, and its relevance for quiescence, have remained elusive. Here, using mouse prostate organoids to model epithelial progenitors, we find that intra-epithelial non-canonical Activin A signalling inhibits cell proliferation in a Smad-independent manner. Mechanistically, Activin A triggers Tak1 and p38 ΜAPK activity, leading to p16 and p21 nuclear import. Spontaneous evasion from this quiescent state occurs upon prolonged culture, due to reduced Ac

SUBMITTER: Dr. Francesco Cambuli 

PROVIDER: S-SCDT-EMBOR-2021-54049-T | biostudies-other |

REPOSITORIES: biostudies-other