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PXD017831

PXD017831 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleFBP1 loss disrupts liver metabolism and promotes tumourigenesis through a hepatic stellate cell senescence secretome
DescriptionCrosstalk between deregulated hepatocyte metabolism and cells within the tumour microenvironment, and consequent effects on liver tumourigenesis, are incompletely understood. We show here that hepatocyte specific loss of the gluconeogenic enzyme fructose 1,6-bisphosphatase 1 (FBP1) disrupts liver metabolic homeostasis and promotes tumour progression. FBP1 is universally silenced in both human and murine liver tumours, and hepatocyte-specific Fbp1 deletion results in steatosis, concomitant with activation and senescence of hepatic stellate cells (HSCs), exhibiting a senescence-associated secretory phenotype (SASP). Depleting senescent HSCs by senolytic treatment with dasatinib/quercetin or ABT-263 inhibits tumour progression. We further demonstrate that FBP1-deficient hepatocytes promote HSC activation by releasing HMGB1; blocking its release with the small molecule inflachromene limits FBP1-dependent HSC activation, subsequent SASP development, and tumour progression. Collectively, these findings provide genetic evidence for FBP1 as a metabolic tumour suppressor in liver cancer and establish a critical link between hepatocyte metabolism and HSC senescence that promotes tumour growth.
HostingRepositoryMassIVE
AnnounceDate2020-03-02
AnnouncementXMLSubmission_2020-05-27_15:32:59.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterHsin-Yao Tang
SpeciesList scientific name: Mus musculus; common name: house mouse; NCBI TaxID: 10090;
ModificationListOxidation; Acetyl
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-03-02 10:29:10ID requested
12020-05-27 15:33:00announced
Publication List
no publication
Keyword List
submitter keyword: TMT-10plex, FBP1, cell senescence secretome, liver metabolism
Contact List
M. Celeste Simon
contact affiliationAbramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania
contact emailceleste2@pennmedicine.upenn.edu
lab head
Hsin-Yao Tang
contact affiliationThe Wistar Institute
contact emailtangh@wistar.org
dataset submitter
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