PXD025902

PXD025902 is an original dataset announced via ProteomeXchange.

Title	SEVERE CONSEQUENCES OF A HIGH-LIPID DIET INCLUDE HYDROGEN SULFIDE DYSFUNCTION AND DISEASE AGGRESSION IN GLIOBLASTOMA
Description	Glioblastoma (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.
HostingRepository	PRIDE
AnnounceDate	2021-05-25
AnnouncementXML	Submission_2021-05-25_09:45:58.366.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Nazmin Bithi
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	biotinylated residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2021-05-09 07:52:48	ID requested
⏵ 1	2021-05-25 09:45:58	announced

Dataset with its publication pending

submitter keyword: Glioblastoma, Cancer Stem Cells, Metabolism, Diet, Hydrogen Sulfide

Christopher Hine
contact affiliation	Cleveland Clinic Lerner Research Institute Cardiovascular and Metabolic Sciences
contact email	hinec@ccf.org
lab head
Nazmin Bithi
contact affiliation	Cleveland Clinic Lerner Research Institute
contact email	bithin@ccf.org
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD025902
     1. Label: PRIDE project
     2. Name: SEVERE CONSEQUENCES OF A HIGH-LIPID DIET INCLUDE HYDROGEN SULFIDE DYSFUNCTION AND DISEASE AGGRESSION IN GLIOBLASTOMA