PXD058156

PXD058156 is an original dataset announced via ProteomeXchange.

Title	Temozolomide Induces Glioblastoma Dedifferentiation into Highly Malignant Stem-like Cells Through Senescence-Associated Reprogramming via HIF1α/HIF2α Regulation
Description	A critical issue is that recurrent glioblastoma multiforme (GBM) after temozolomide (TMZ) exposure becomes more malignant, exhibiting higher invasion and stemness than the primary tumor. However, the detailed mechanism remains to be elucidated. While the majority of GBM cells succumb to TMZ treatment, some enter cell cycle arrest, adopt a senescence-associated secretory phenotype (SASP), and activate senescence-related signaling pathways. These cells later exit senescence, re-enter the cell cycle, and proliferate, forming aggregates with stemness characteristics, including high expression of stemness markers, colony formation, high invasion, migration, and chemotherapy resistance. Critically, these new aggregates promote the invasion, migration, and chemotherapy resistance of surrounding cells. Gene Set Enrichment Analysis (GSEA) and KEGG analysis of miRNA and mRNA sequences indicated that hallmark-hypoxia and HIF1-signaling pathways were activated. We verified that HIF1α and HIF2α levels changed before, during, and after TMZ treatment. Knocking out HIF1α and HIF2α in GBM cells and exposing them to TMZ resulted in fewer senescent cells and aggregates. This study clarifies how recurrent GBM becomes more malignant during and after TMZ treatment and highlights the regulatory roles of HIF1α and HIF2α, emphasizing that preventing senescence cell formation and inhibiting HIF1α and HIF2α expression are crucial for improving therapeutic outcomes.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-07_05:05:17.455.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Liao Bin
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-11-21 19:24:22	ID requested
⏵ 1	2025-05-07 05:05:18	announced

10.1038/s41419-025-07617-w;

Wang P, Liao B, Gong S, Guo H, Zhao L, Liu J, Wu N, regulation. Cell Death Dis, 16(1):317(2025) [pubmed]

submitter keyword: temozolomide,glioblastoma

Bin Liao
contact affiliation	Department of Neurosurgery, Chongqing Research Center for Glioma Precision Medicine, Chongqing General Hospital, Chongqing University
contact email	liaobin12@cqu.edu.cn
lab head
Liao Bin
contact affiliation	Department of Neurosurgery, Chongqing general Hospital, Chongqing University, Chongqing
contact email	liaobin12@cqu.edu.cn
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/PXD058156

PRIDE project URI

• PRIDE
  1. PXD058156
     1. Label: PRIDE project
     2. Name: Temozolomide Induces Glioblastoma Dedifferentiation into Highly Malignant Stem-like Cells Through Senescence-Associated Reprogramming via HIF1α/HIF2α Regulation