PXD028271

PXD028271 is an original dataset announced via ProteomeXchange.

Title	Chromosomal instability adaptation dependencies confer unique targetable vulnerabilities in therapy refractory lethal prostate cancer
Description	Chromosomal instability (CIN), an ongoing rate of chromosome missegregation during mitosis, is a defining feature of cancer. However, high chromosomal aberrations are detrimental for cell fitness. Here we investigated mechanisms allowing lethal prostate cancer (PCa) to tolerate and survive increasing CIN. Transcriptomic and proteomic analysis of patient datasets and experimental models showed a concomitant increase of CIN and cell division fidelity kinases in lethal PCa. Functional studies identified MASTL as a key kinase to which therapy-resistant PCa cells become addicted to restrain lethal CIN and ensure survival. Combined analysis of transcription factors increased in high CIN PCa patient datasets with detailed promoter analysis identified that MASTL expression is regulated by the Androgen Receptor variant 7 (AR-V7) and E2F7. Finally, targeting MASTL addiction vulnerability in vivo using the small molecule inhibitor GKI-1, improves survival of pre-clinical models. These findings provide proof-of-concept for exploiting CIN levels as a therapeutic approach in cancer.
HostingRepository	PRIDE
AnnounceDate	2023-01-14
AnnouncementXML	Submission_2023-01-14_04:05:43.677.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	ZhuoningLi
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-09-09 08:09:23	ID requested
⏵ 1	2023-01-14 04:05:44	announced

Dataset with its publication pending

submitter keyword: MASTL expression,Chromosomal instability

VeronicaRodriguez-Bravo
contact affiliation	Cancer Biology Department, Sidney Kimmel Cancer Center, Thomas Jefferson University
contact email	Veronica.Rodriguez-Bravo@jefferson.edu
lab head
ZhuoningLi
contact affiliation	MSKCC
contact email	liz2@mskcc.org
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD028271
     1. Label: PRIDE project
     2. Name: Chromosomal instability adaptation dependencies confer unique targetable vulnerabilities in therapy refractory lethal prostate cancer