PXD061009-1

PXD061009 is an original dataset announced via ProteomeXchange.

Title	GSC 2907 SRGN IP mass spectrometry
Description	Glioblastoma (GBM) is a highly lethal primary malignant brain tumor. The high level of heterogeneity within GBM inevitably leads to treatment resistance and tumor recurrence. Glioblastoma stem cells (GSCs) contribute to the distinct properties of GBM through their contribution to therapeutic resilience. Here, we found that enhanced classical (CL) and mesenchymal (MES) transcriptional signatures were associated with poor patient prognosis. Through the integrated analyses of single-cell RNA sequencing and clinical datasets, we identified specific brain tumor targets, including MEOX2 for the CL subtype and SRGN for the MES subtype respectively. MEOX2 sustained the CL subtype signature and played a particular role in CL GSCs by activating Notch signaling. SRGN maintained the MES phenotype and regulated the NF-κB signaling by preventing NFKB1 from proteasomal degradation. Both genetic and pharmacologic treatments showed that CL GSCs were preferentially sensitive to the inhibition of MEOX2, while MES GSCs were more susceptible to SRGN. We further screend FDA-approved drugs with MEOX2 and SRGN targeting capabilities as candidates for further investigation. Combined CL and MES targeting demonstrated enhanced efficacy, both in vitro and in vivo. Collectively, our results elucidated the mechanism of GBM heterogeneity, and highlighted a therapeutic strategy for the elimination of heterogeneous cellular populations through combinatorial targeting of MEOX2 and SRGN in GSCs.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-07_07:27:16.094.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xiuxing Wang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-20 09:10:50	ID requested
⏵ 1	2025-05-07 07:27:17	announced

Lu C, Kang T, Zhang J, Yang K, Liu Y, Song K, Lin Q, Dixit D, Gimple RC, Zhang Q, Shi Z, Fan X, Wu Q, Li D, Shan D, Gao J, Gu D, You H, Li Y, Yang J, Zhao L, Qiu Z, Yang H, Zhao N, Gao W, Tao W, Lu Y, Chen Y, Ji J, Zhu Z, Kang C, Man J, Agnihotri S, Wang Q, Lin F, Qian X, Mack SC, Hu Z, Li C, Taylor MD, Liu N, Zhang N, Lu M, You Y, Rich JN, Zhang W, Wang X, Combined targeting of glioblastoma stem cells of different cellular states disrupts malignant progression. Nat Commun, 16(1):2974(2025) [pubmed]

10.1038/s41467-025-58366-5;

submitter keyword: Human GSC SRGN MS

Xiuxing Wang
contact affiliation	Nanjing Medical University
contact email	drxiuxingwang@163.com
lab head
Xiuxing Wang
contact affiliation	Nanjing Medical University
contact email	drxiuxingwang@163.com
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/2025/05/PXD061009

PRIDE project URI

• PRIDE
  1. PXD061009
     1. Label: PRIDE project
     2. Name: GSC 2907 SRGN IP mass spectrometry