PXD012971

PXD012971 is an original dataset announced via ProteomeXchange.

Title	RET Kinase Inhibition in Neuroendocrine Prostate Cancer, part 2
Description	Increased treatment of metastatic castration resistant prostate cancer (mCRPC) with second-generation anti-androgen therapies (ADT) has coincided with a greater incidence of lethal, aggressive variant prostate cancer (AVPC) tumors that have lost androgen receptor (AR) signaling. AVPC tumors may also express neuroendocrine markers, termed neuroendocrine prostate cancer (NEPC). Recent evidence suggests kinase signaling may be an important driver of NEPC. To identify targetable kinases in NEPC, we performed global phosphoproteomics comparing AR-negative to AR-positive prostate cancer cell lines and identified multiple altered signaling pathways, including enrichment of RET kinase activity in the AR-negative cell lines. Clinical NEPC and NEPC patient derived xenografts displayed upregulated RET transcript and RET pathway activity. Pharmacologically inhibiting RET kinase in NEPC models dramatically reduced tumor growth and cell viability in mouse and human NEPC models. Our results suggest that targeting RET in NEPC tumors with high RET expression may be a novel treatment option.
HostingRepository	PRIDE
AnnounceDate	2020-06-02
AnnouncementXML	Submission_2020-06-02_09:07:53.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Zoi Sychev
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-03-05 05:42:14	ID requested
⏵ 1	2020-06-02 09:07:54	announced

VanDeusen HR, Ramroop JR, Morel KL, Bae SY, Sheahan AV, Sychev Z, Lau NA, Cheng LC, Tan VM, Li Z, Petersen A, Lee JK, Park JW, Yang R, Hwang JH, Coleman I, Witte ON, Morrissey C, Corey E, Nelson PS, Ellis L, Drake JM, Targeting RET Kinase in Neuroendocrine Prostate Cancer. Mol Cancer Res, 18(8):1176-1188(2020) [pubmed]

curator keyword: Biomedical

submitter keyword: Prostate cancer, RET, kinase, phosphoproteomics, human

Zoi Sychev
contact affiliation	University of Minnesota, Twin-Cities, Pharmacology Department
contact email	zsychev@umn.edu
lab head
Zoi Sychev
contact affiliation	University of Minnesota at Minneapolis
contact email	zsychev@umn.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/2020/05/PXD012971

PRIDE project URI

• PRIDE
  1. PXD012971
     1. Label: PRIDE project
     2. Name: RET Kinase Inhibition in Neuroendocrine Prostate Cancer, part 2