PXD042059 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Nuclear lamin A/C phosphorylation by loss of Androgen Receptor is a global determinant of cancer-associated fibroblast activation |
Description | 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 with increased micronuclei formation and frequent ruptures, with similar alterations occurring in fully established CAFs. 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 protein phosphatase PPP1. In parallel with a decreased lamin-PPP1 association, AR loss results in a marked increase of lamin A/C phosphorylation at Ser 301, which is also a feature of CAFs. Phospho-Ser301 Lamin A/C binds to the transcription promoter regulatory region of multiple CAF marker genes upregulated by AR loss, and expression of a lamin A/CSer301 phosphomimetic mutant is sufficient for conversion of normal fibroblasts into tumor-promoting CAFs. The findings point to an AR - lamin A/C - PPP1 axis and lamin A/C phosphorylation at ser 301 as critical determinants of CAF activation. |
HostingRepository | PRIDE |
AnnounceDate | 2024-08-12 |
AnnouncementXML | Submission_2024-08-12_03:16:30.400.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD042059 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | Patrice Waridel |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Q Exactive Plus |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-05-08 08:25:41 | ID requested | |
⏵ 1 | 2024-08-12 03:16:30 | announced | |
Publication List
Keyword List
submitter keyword: Human, cancer-associated fibroblasts, androgen receptor |
Contact List
Gian-Paolo Dotto |
contact affiliation | Dept. of Immunobiology, University of Lausanne, Switzerland |
contact email | paolo.dotto@unil.ch |
lab head | |
Patrice Waridel |
contact affiliation | University of Lausanne |
contact email | patrice.waridel@unil.ch |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD042059
- Label: PRIDE project
- Name: Nuclear lamin A/C phosphorylation by loss of Androgen Receptor is a global determinant of cancer-associated fibroblast activation