PXD015783

PXD015783 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2019-10-11 01:17:07	ID requested
⏵ 1	2020-02-19 03:26:44	announced

Dataset with its publication pending

submitter keyword: Human, High-Grade Serous Ovarian Carcinoma, MRCKA, CDC42BPA

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

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/2020/02/PXD015783

PRIDE project URI

• PRIDE
  1. PXD015783
     1. Label: PRIDE project
     2. Name: Identification of MRCKA as an integral component of ovarian cancer signaling and a therapeutic target