PXD017831-1
PXD017831 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | FBP1 loss disrupts liver metabolism and promotes tumourigenesis through a hepatic stellate cell senescence secretome |
| Description | Crosstalk 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. |
| HostingRepository | MassIVE |
| AnnounceDate | 2020-03-02 |
| AnnouncementXML | Submission_2020-05-27_15:32:59.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Hsin-Yao Tang |
| SpeciesList | scientific name: Mus musculus; common name: house mouse; NCBI TaxID: 10090; |
| ModificationList | Oxidation; Acetyl |
| Instrument | Q Exactive HF |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2020-03-02 10:29:10 | ID requested | |
| ⏵ 1 | 2020-05-27 15:33:00 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: TMT-10plex, FBP1, cell senescence secretome, liver metabolism |
Contact List
| M. Celeste Simon | |
|---|---|
| contact affiliation | Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania |
| contact email | celeste2@pennmedicine.upenn.edu |
| lab head | |
| Hsin-Yao Tang | |
| contact affiliation | The Wistar Institute |
| contact email | tangh@wistar.org |
| dataset submitter | |
Full Dataset Link List
| MassIVE dataset URI |
| 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://massive.ucsd.edu/MSV000085045/ |
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