PXD046446 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Proteomic and phosphoproteomic analysis 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_04:30:02.105.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 | phosphorylated residue |
Instrument | Q Exactive HF |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-10-27 04:33:16 | ID requested | |
⏵ 1 | 2024-03-26 04:30:02 | announced | |
Publication List
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] |
Keyword List
submitter keyword: breast cancer,human |
Contact List
Emma Nimèus |
contact affiliation | Lund University |
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD046446
- Label: PRIDE project
- Name: Proteomic and phosphoproteomic analysis of ESR1 mutant cells