PXD032369

PXD032369 is an original dataset announced via ProteomeXchange.

Title	Proteomic characterization of ESR1 mutant cells
Description	Three quarters of all breast cancer cases express the estrogen receptor (ER, ESR1 gene), which promotes tumor growth and constitutes a direct target for endocrine therapies. ESR1 mutations have been implicated in therapy resistance in metastatic breast cancers, in particular to aromatase inhibitors. ESR1 mutations promote constitutive ER activity and affect other signaling pathways, allowing cancer cells to proliferate by employing mechanisms within and outwith direct regulation by the ER. Although subjected to extensive genetic and transcriptomic analyses, understanding of protein alterations remains poorly investigated. Towards this, we employed an integrated mass spectrometry (MS) based proteomic approach to profile the protein and phosphoprotein differences in breast cancer cell lines expressing the frequent Y537N and Y537S ER mutations. Global proteome analysis revealed enrichment of mitotic and immune signaling pathways in ER mutant cells, while phosphoprotein analysis evidenced enriched activity of proliferation associated kinases, in particular CDKs and MTOR. Integration of protein expression and phosphorylation data revealed pathway-dependent discrepancies (motility vs proliferation) that were observed at varying degrees across mutant and wt ER cells. Additionally, protein expression and phosphorylation patterns, while under different regulation, still recapitulated the estrogen-independent phenotype of ER mutant cells.
HostingRepository	PRIDE
AnnounceDate	2024-03-26
AnnouncementXML	Submission_2024-03-26_03:15:16.435.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tommaso De Marchi
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-03-17 09:33:19	ID requested
⏵ 1	2024-03-26 03:15:17	announced

10.1038/s41598-024-56412-8;

De Marchi T, Lai CF, Simmons GM, Goldsbrough I, Harrod A, Lam T, Buluwela L, Kjellstr, ö, m S, Brueffer C, Saal LH, Malmstr, ö, m J, Ali S, Nim, é, us E, Proteomic profiling reveals that ESR1 mutations enhance cyclin-dependent kinase signaling. Sci Rep, 14(1):6873(2024) [pubmed]

submitter keyword: ESR1 mutation,breast cancer

Emma Nimeus
contact affiliation	Division of Surgery, Oncology, and Pathology, Department of Clinical Sciences, Lund University, Solvegatan 19, 223 62, Lund, Sweden.
contact email	emma.nimeus@med.lu.se
lab head
Tommaso De Marchi
contact affiliation	Lund University
contact email	tommaso.de_marchi@med.lu.se
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/03/PXD032369

PRIDE project URI

• PRIDE
  1. PXD032369
     1. Label: PRIDE project
     2. Name: Proteomic characterization of ESR1 mutant cells