PXD039264

PXD039264 is an original dataset announced via ProteomeXchange.

Title	Integration of Proteomics, Phosphoproteomics and Loss-of-function Screen Identifies WEE1 Inhibition as a Combination Therapy with Dasatinib against Proneural Glioblastoma.
Description	Background: Glioblastoma (GB) is the most common primary malignancy of the central nervous system. It can be classified into proneural (PN), mesenchymal (MES) and classical (CL) based on transcriptomics. Due to increased resistance against targeted therapies, such as the PN subtype and dasatinib, identification of combination therapies is of great interest. Methods: Proteomics and phosphoproteomics data were collected from dasatinib inhibited glioblastoma stem cells (GSCs). Additionally, a pooled shRNA loss-of-function viability screen was utilized to identify genes whose knockdown sensitizes GSCs to dasatinib. These data, along with existing transcriptomics data, were computationally integrated using a novel modification of the SamNet algorithm (SamNet 2.0) for network flow learning to identify potential combination therapies. In vitro viability assays were used to verify synergy of potential combinations. Results: Using omics data and the pooled shRNA screen, the cell cycle protein WEE1 was identified as a potential combination therapy target for PN GSCs. Validation experiments showed a robust synergistic effect through combination of dasatinib and the WEE1 inhibitor, MK-1775, in PN GSCs. Combined inhibition using dasatinib and MK-1775 propagated DNA damage in PN GCSs, with GCSs showing a differential subtype-driven pattern of expression of cell cycle genes in TCGA RNA-Seq data.
HostingRepository	PRIDE
AnnounceDate	2026-01-12
AnnouncementXML	Submission_2026-01-12_00:05:40.355.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Obada Alhalabi
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2023-01-05 01:46:41	ID requested
⏵ 1	2026-01-12 00:05:41	announced

10.1016/j.canlet.2024.217265;

Alhalabi OT, G, ö, ttmann M, Gold MP, Schlue S, Hielscher T, Iskar M, Kessler T, Hai L, Lokumcu T, Cousins CC, Herold-Mende C, He, ß, ling B, Horschitz S, Jabali A, Koch P, Baumgartner U, Day BW, Wick W, Sahm F, Krieg SM, Fraenkel E, Phillips E, Goidts V, Integration of transcriptomics, proteomics and loss-of-function screening reveals WEE1 as a target for combination with dasatinib against proneural glioblastoma. Cancer Lett, 605():217265(2024) [pubmed]

submitter keyword: WEE1, Dasatinib,Glioblastoma, SILAC

Violaine Goidts
contact affiliation	Brain tumor translational targets German Cancer Research Center (DKFZ) Im Neuenheimer Feld 580 69120 Heidelberg Germany
contact email	v.goidts@dkfz-heidelberg.de
lab head
Obada Alhalabi
contact affiliation	Heidelberg Univestiy Hospital German Cancer Research Center (DKFZ)
contact email	obadath@hotmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD039264
     1. Label: PRIDE project
     2. Name: Integration of Proteomics, Phosphoproteomics and Loss-of-function Screen Identifies WEE1 Inhibition as a Combination Therapy with Dasatinib against Proneural Glioblastoma.