PXD035936-1

PXD035936 is an original dataset announced via ProteomeXchange.

Title	MAF amplification licenses Estrogen Receptor Alpha to drive breast cancer metastasis
Description	MAF-amplification increases the risk of breast cancer (BCa) metastasis through poorly understood mechanisms but with important clinical implications. Estrogen receptor-positive (ER+) BCa associated with estrogen (E2) dependency sustains growth of early of breast carcinomas, but ultimately, supports metastasis by unknown mechanisms. Here we integrate proteomics, (epi)genomics and functional assays derived from human and syngeneic BCa mouse models to show that MAF directly interacts with ERalpha, thereby promoting a unique chromatin state that favors the metastatic spread of ER+ BCa cells. Indeed, we identify a set of metastasis-promoting genes that are de novo licenced following EERa2-exposure in a MAF-dependent manner. Among these we found factors influence the establishment of cellular identity and with a known role in metastasis initiation (e.g. SOX9), as well as modulators of the bone stroma, which can ultimately aid in preparing the bone metastatic “soil” (e.g. FGF18, PTHLH and JAG1). Central to the epigenomic remodeling that facilitates the expression of the MAF/E2 gene set is the histone demethylase KDM1A. Indeed, loss of KDM1A activity prevents MAF/E2-mediated BCa metastasis. Collectively, here we disentangle the molecular framework that underlies MAF/E2-mediated metastasis and demonstrate that genetic, epigenetic and hormonal systemic cues are integrated in BCa cells to determine their metastatic success, and with it patient prognosis.
HostingRepository	PRIDE
AnnounceDate	2023-11-13
AnnouncementXML	Submission_2023-11-13_12:40:36.998.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	MartaVilaseca
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-08-10 09:04:20	ID requested
⏵ 1	2023-11-13 12:40:37	announced
2	2023-11-14 07:27:34	announced	2023-11-14: Updated project metadata.
3	2024-10-22 06:14:02	announced	2024-10-22: Updated project metadata.

submitter keyword: Estrogen signaling,Breast cancer, Metastasis, MAF

RogerGomis
contact affiliation	Institute for Research in Biomedicine, Baldiri i Reixac 10, Barcelona 08028, Spain
contact email	roger.gomis@irbbarcelona.org
lab head
MartaVilaseca
contact affiliation	Mass Spectrometry & Proteomics Core Facility (MSPCF) Institute for Research in Biomedicine (IRB Barcelona) Barcelona Institute of Science and Technology (BIST) C/ Baldiri Reixac, 10-12 08028 Barcelona - Spain
contact email	masspe@irbbarcelona.org
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD035936
     1. Label: PRIDE project
     2. Name: MAF amplification licenses Estrogen Receptor Alpha to drive breast cancer metastasis