Academic Journal
Nuclear lamin A/C phosphorylation by loss of androgen receptor leads to cancer-associated fibroblast activation
| Title: | Nuclear lamin A/C phosphorylation by loss of androgen receptor leads to cancer-associated fibroblast activation |
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| Authors: | Soumitra Ghosh, Jovan Isma, Paola Ostano, Luigi Mazzeo, Annagiada Toniolo, Monalisa Das, Joni R. White, Christian Simon, G. Paolo Dotto |
| Source: | Nat Commun Nature Communications, Vol 15, Iss 1, Pp 1-22 (2024) Nature communications, vol. 15, no. 1, pp. 7984 |
| Publisher Information: | Springer Science and Business Media LLC, 2024. |
| Publication Year: | 2024 |
| Subject Terms: | Cell Nucleus, Male, Nuclear Envelope, Science, Fibroblasts, Lamin Type A, Article, Cancer-Associated Fibroblasts, Receptors, Androgen, Protein Phosphatase 1, 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, Tumor Microenvironment |
| Description: | 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. |
| Document Type: | Article Other literature type |
| File Description: | application/pdf |
| Language: | English |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-024-52344-z |
| Access URL: | https://pubmed.ncbi.nlm.nih.gov/39266569 https://doaj.org/article/ecacd5c27cbc40799626a289a8be3460 http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_39467E97F3A55 https://serval.unil.ch/resource/serval:BIB_39467E97F3A5.P001/REF.pdf https://serval.unil.ch/notice/serval:BIB_39467E97F3A5 |
| Rights: | CC BY NC ND |
| Accession Number: | edsair.doi.dedup.....4a96361c65e17c1bd68796d0f84143b6 |
| Database: | OpenAIRE |
| ISSN: | 20411723 |
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| DOI: | 10.1038/s41467-024-52344-z |