PXD021635

PXD021635 is an original dataset announced via ProteomeXchange.

Title	Disruption of splicing, proliferation and stemness via PRMT5 inhibition as a therapeutic strategy for GBM
Description	Glioblastoma (GBM) is a deadly cancer in which cancer stem cells (CSCs) sustain tumor growth and contribute to therapeutic resistance. Protein Arginine Methyltransferase 5 (PRMT5) has recently emerged as a promising target in GBM. Using two orthogonal-acting inhibitors of PRMT5 (GSK591 or LLY-283), we show that pharmacological inhibition of PRMT5 suppresses the growth of a cohort of 46 patient-derived GBM stem cell cultures, with the proneural subtype showing greater sensitivity. We show that PRMT5 inhibition caused widespread disruption of splicing across the transcriptome, particularly affecting cell cycle gene products. We identify a GBM splicing signature that correlates with the degree of response to PRMT5 inhibition. Importantly, we demonstrate that LLY-283 is brain-penetrant and significantly prolongs the survival of mice with orthotopic patient-derived xenografts. Collectively, our findings provide a rationale for the clinical development of brain penetrant PRMT5 inhibitors as treatment for GBM.
HostingRepository	PRIDE
AnnounceDate	2020-11-03
AnnouncementXML	Submission_2020-11-03_03:44:49.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Eric Bonneil
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; acetylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2020-09-22 10:16:34	ID requested
⏵ 1	2020-11-03 03:44:50	announced

Dataset with its publication pending

submitter keyword: glioblastoma, proteomics, PRMT5 inhibition, cancer

Mike Tyers
contact affiliation	IRIC-Université de Montréal
contact email	mike.tyers@umontreal.ca
lab head
Eric Bonneil
contact affiliation	Proteomic Platform
contact email	eric.bonneil@umontreal.ca
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD021635
     1. Label: PRIDE project
     2. Name: Disruption of splicing, proliferation and stemness via PRMT5 inhibition as a therapeutic strategy for GBM