PXD020357 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Kinome Profiling of Primary Endometrial Tumors Using Multiplexed Inhibitor Beads and Mass Spectrometry Identifies SRPK1 As A Candidate Therapeutic Target |
Description | Protein kinases (collectively termed the kinome) represent one of the most tractable drug targets in the pursuit of new and effective cancer treatments. However, less than 20% of the kinome is currently being explored as primary targets for cancer therapy, leaving the majority of the kinome untargeted for drug therapy. Chemical proteomics approaches such as Multiplexed Inhibitor Beads and Mass Spectrometry (MIB-MS) have been developed that measure the abundance of a significant proportion of the kinome, providing a strategy to interrogate kinome landscapes and dynamics. Kinome profiling of cancer cell lines using MIB-MS has been extensively characterized, however, the application of this method to measure tissue kinome(s) has not been thoroughly explored. Here, we present a quantitative proteomics workflow specifically designed for kinome profiling of tissues that pairs MIB-MS with a newly designed s-SILAC kinome standard. Using this workflow, we mapped the kinome landscape of endometrial carcinoma (EC) tumors and normal endometrial (NE) tissues and identified several kinases overexpressed in EC tumors, including Serine/Arginine-Rich Splicing Factor kinase, (SRPK1). Immunohistochemical (IHC) analysis of EC tumor TMAs confirmed MIB-MS findings and showed SRPK1 protein levels were highly expressed in endometrioid and uterine serous cancer (USC) histological subtypes. Querying large-scale genomics studies of EC tumors revealed high expression of SRPK1 correlated with poor survival. Inhibition of SRPK1 in USC cells altered mRNA splicing, downregulating several oncogenes including MYC and Survivin resulting in apoptosis. Taken together, we present a SILAC-based MIB-MS kinome profiling platform for measuring kinase abundance in tumor tissues, and demonstrate its application to identify SRPK1 as a plausible kinase drug target for the treatment of EC. |
HostingRepository | PRIDE |
AnnounceDate | 2020-09-30 |
AnnouncementXML | Submission_2020-10-12_06:53:34.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | James Duncan |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | 6x(13)C labeled residue; iodoacetamide derivatized residue |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-07-14 04:08:03 | ID requested | |
1 | 2020-09-30 01:04:11 | announced | |
⏵ 2 | 2020-10-12 06:53:35 | announced | 2020-10-12: Updated publication reference for PubMed record(s): 32994315. |
Publication List
Kurimchak AM, Kumar V, Herrera-Mont, รก, vez C, Johnson KJ, Srivastava N, Davarajan K, Peri S, Cai KQ, Mantia-Smaldone GM, Duncan JS, Kinome Profiling of Primary Endometrial Tumors Using Multiplexed Inhibitor Beads and Mass Spectrometry Identifies SRPK1 as Candidate Therapeutic Target. Mol Cell Proteomics, 19(12):2068-2090(2020) [pubmed] |
Keyword List
submitter keyword: Endometrial, SRPK1 |
Contact List
James Stuart Duncan |
contact affiliation | Cancer Biology Department, Fox Chase Cancer Center, Philadelphia, PA, USA |
contact email | james.s.duncan@fccc.edu |
lab head | |
James Duncan |
contact affiliation | Fox Chase Cancer Center |
contact email | james.s.duncan@fccc.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD020357
- Label: PRIDE project
- Name: Kinome Profiling of Primary Endometrial Tumors Using Multiplexed Inhibitor Beads and Mass Spectrometry Identifies SRPK1 As A Candidate Therapeutic Target