PXD015783 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Identification of MRCKA as an integral component of ovarian cancer signaling and a therapeutic target |
Description | High-grade serous ovarian carcinoma (HGSOC) is the most lethal gynecological cancer with few effective targeted therapies. HGSOC tumors exhibit genomic instability with frequent alterations in the protein kinome; however, only a small fraction of the kinome has been therapeutically targeted in HGSOC. Using multiplexed inhibitor beads and mass spectrometry (MIB-MS), we mapped the kinome landscape of HGSOC patient tumors and tumors isolated from HGSOC patient-derived xenograft (PDX) models. Kinome profiling of HGSOC tumors uncovered a prevalent MIB-MS kinome signature consisting of established HGSOC driver kinases, as well as several kinases previously unexplored in HGSOC. Loss-of-function analysis targeting the tumor kinome signature in HGSOC cells nominated CDC42BPA (also known as MRCKA) as a putative therapeutic target. Characterization of MRCKA knockdown in established HGSOC cell lines demonstrated MRCKA was integral to signaling that regulated the cell cycle checkpoint and focal adhesion/ actin remodeling, and depletion of MRCKA impaired cell migration, proliferation and survival. Moreover, small molecule inhibition of MRCKA using BDP9066 inhibited cell growth and induced apoptosis in HGSOC cells, as well as blocked spheroid formation, supporting MRCKA as a novel therapeutic target for the treatment of HGSOC. |
HostingRepository | PRIDE |
AnnounceDate | 2020-02-19 |
AnnouncementXML | Submission_2020-02-19_03:26:43.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; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2019-10-11 01:17:07 | ID requested | |
⏵ 1 | 2020-02-19 03:26:44 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Human, High-Grade Serous Ovarian Carcinoma, MRCKA, CDC42BPA |
Contact List
James Stuart Duncan |
contact affiliation | Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, PA, USA |
contact email | james.duncan2@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
- PXD015783
- Label: PRIDE project
- Name: Identification of MRCKA as an integral component of ovarian cancer signaling and a therapeutic target