PXD001680 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | A common cell state in Triple Negative Breast Cancers can be targeted through inhibition of Spleen Tyrosine Kinase (SYK) |
Description | Breast tumors are highly heterogeneous and for many molecular subtypes no targeted therapies are available. These include breast cancers that display hallmarks of epithelial to mesenchymal transition (EMT), a process related to metastasis and enriched in triple negative breast cancers (TNBCs). To determine whether this EMT cellular state could be therapeutically exploited, we performed a large-scale chemical genetic screen. We identified a group of structurally related compounds, including the clinically advanced drug PKC412 (midostaurin), that targeted post-EMT breast cancer cells. PKC412 induced apoptosis specifically in basal-like TNBC cells and inhibited tumor growth in vivo. Structure activity relationship (SAR) studies, chemical proteomics, and computational modeling identified the kinase SYK as a critical PKC412 target. Specific SYK inhibitors and PKC412 displayed a similar profile across a large panel of breast cancer cell lines, indicating a shared mode of action. Phosphoproteomics analysis revealed that SYK activates STAT3, and chemical or genetic inhibition of STAT3 resulted in cell death in basal-like breast cancer cells. This non-oncogene addiction of basal-like breast cancer cells to SYK suggests that chemical SYK inhibition may be beneficial for a specific subset of triple negative breast cancer patients. |
HostingRepository | PRIDE |
AnnounceDate | 2016-06-15 |
AnnouncementXML | Submission_2016-06-15_08:07:39.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Andre Mueller |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | phosphorylated residue |
Instrument | LTQ Orbitrap Velos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2015-01-14 08:33:10 | ID requested | |
⏵ 1 | 2016-06-15 08:07:40 | announced | |
Publication List
Muellner MK, Mair B, Ibrahim Y, Kerzendorfer C, Lechtermann H, Trefzer C, Klepsch F, M, ΓΌ, ller AC, Leitner E, Macho-Maschler S, Superti-Furga G, Bennett KL, Baselga J, Rix U, Kubicek S, Colinge J, Serra V, Nijman SM, Targeting a cell state common to triple-negative breast cancers. Mol Syst Biol, 11(1):789(2015) [pubmed] |
Keyword List
curator keyword: Biomedical |
submitter keyword: Human breast cancer, SYK inhibition, phosphotyrosine proteomics |
Contact List
Keiryn L. Bennett |
contact affiliation | CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences Lazarettgasse 14, AKH BT 25.3 1090 Vienna, Austria |
contact email | kbennett@cemm.oeaw.ac.at |
lab head | |
Andre Mueller |
contact affiliation | Research Center for Molecular Medicine of the Austrian Academy of Sciences |
contact email | amueller@cemm.oeaw.ac.at |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD001680
- Label: PRIDE project
- Name: A common cell state in Triple Negative Breast Cancers can be targeted through inhibition of Spleen Tyrosine Kinase (SYK)