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PXD044773-1

PXD044773 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleCell-specific crosstalk proteomics reveals cathepsin B signaling as a driver of glioblastoma malignancy near the subventricular zone
DescriptionGlioblastoma (GBM) is the most prevalent and aggressive malignant primary brain tumor. GBM proximal to the lateral ventricles (LVs) is more aggressive, potentially due to subventricular zone (SVZ) contact. Despite this, crosstalk between GBM and neural stem/progenitor cells (NSC/NPCs) is not well understood. Using cell-specific proteomics, we show that LV-proximal GBM prevents neuronal maturation of NSCs through induction of senescence. Additionally, interaction with NPCs increases cathepsin B (CTSB) expression in GBM brain tumor initiating cells (BTICs). Lentiviral knockdown and recombinant protein experiments reveal both cell-intrinsic and soluble CTSB promote malignancy-associated BTIC phenotypes. Soluble CTSB stalls neuronal maturation in NPCs while promoting senescence, providing a link between LV-tumor proximity and neurogenesis disruption. Finally, we show LV-proximal CTSB upregulation in patients, showing the relevance of this crosstalk in human GBM biology. These results demonstrate the value of proteomic analysis in tumor microenvironment research and provide direction for new therapeutic strategies in GBM.
HostingRepositoryPRIDE
AnnounceDate2024-06-24
AnnouncementXMLSubmission_2024-06-23_19:26:55.986.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterTuKiet Lam
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue; acetylated residue; monohydroxylated residue; deaminated residue; iodoacetamide derivatized residue
InstrumentQ Exactive Plus
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-08-23 01:46:55ID requested
12024-06-23 19:26:56announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: MetRS L274G, glioma, proteomics, lateral ventricle, stem cell niche, subventricular zone,brain cancer, neurogenesis, click chemistry, senescence
Contact List
TuKiet Lam
contact affiliationKeck MS & Proteomics Resource Yale School of Medicine
contact emailtukiet.lam@yale.edu
lab head
TuKiet Lam
contact affiliationYale University
contact emailtukiet.lam@yale.edu
dataset submitter
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Dataset FTP location
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