PXD042059-1

PXD042059 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2023-05-08 08:25:41	ID requested
⏵ 1	2024-08-12 03:16:30	announced

10.6019/PXD042059;

submitter keyword: Human, cancer-associated fibroblasts, androgen receptor

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

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PRIDE project URI

• PRIDE
  1. PXD042059
     1. Label: PRIDE project
     2. Name: Nuclear lamin A/C phosphorylation by loss of Androgen Receptor is a global determinant of cancer-associated fibroblast activation