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PXD023685-1

PXD023685 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleSEVERE CONSEQUENCES OF A HIGH-LIPID DIET INCLUDE HYDROGEN SULFIDE DYSFUNCTION AND DISEASE AGGRESSION IN GLIOBLASTOMA
DescriptionGlioblastoma (GBM) remains among the deadliest of human malignancies, and the emergence of the cancer stem cell (CSC) phenotype represents a major challenge to durable treatment response. Because the environmental and lifestyle factors that impact CSC populations are not clear, we sought to understand the consequences of diet on CSC enrichment. We evaluated disease progression in mice fed an obesity-inducing high-fat diet (HFD) versus a low-fat, control diet. HFD resulted in hyper-aggressive disease accompanied by CSC enrichment and shortened survival. HFD drove intracerebral accumulation of saturated fats, which inhibited the production of the cysteine metabolite and gasotransmitter, hydrogen sulfide (H2S). H2S functions principally through protein S-sulfhydration and regulates multiple programs including bioenergetics and metabolism. Inhibition of H2S increased proliferation and chemotherapy resistance, whereas treatment with H2S donors led to death of cultured GBM cells and stasis of GBM tumors in vivo. GBM specimens present an overall reduction in protein S-sulfhydration, primarily associated with proteins regulating cellular metabolism. These findings provide new evidence that diet modifiable H2S signaling serves to suppress GBM by restricting metabolic fitness, while its loss triggers CSC enrichment and disease acceleration. Interventions augmenting H2S bioavailability concurrent with GBM standard of care may improve outcomes for GBM patients.
HostingRepositoryPRIDE
AnnounceDate2021-05-25
AnnouncementXMLSubmission_2021-05-25_09:49:00.577.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD023685
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterNazmin Bithi
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListbiotinylated residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-01-19 22:31:02ID requested
12021-05-25 09:49:00announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Glioblastoma, Cancer Stem Cells, Metabolism, Diet, Hydrogen Sulfide
Contact List
Christopher Hine
contact affiliationCleveland Clinic Lerner Research Institute
contact emailhinec@ccf.org
lab head
Nazmin Bithi
contact affiliationCleveland Clinic Lerner Research Institute
contact emailbithin@ccf.org
dataset submitter
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Dataset FTP location
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