PXD016630

PXD016630 is an original dataset announced via ProteomeXchange.

Title	HIF-1α and HIF-2α differently regulate tumour development, metabolism and inflammation of clear cell renal cell carcinoma in mice
Description	Mutational inactivation of VHL is the earliest genetic event in the majority of ccRCCs, leading to activation of the HIF-1α and HIF-2α transcription factors. While correlative studies of human ccRCCs and functional studies using human ccRCC cell lines have implicated HIF-1α as an inhibitor and HIF-2α as a promoter of aggressive tumour behaviours, their roles in tumour onset have not been functionally addressed. Using an autochthonous ccRCC model, we show genetically that Hif1a is necessary for tumour formation whereas Hif2a deletion has only minor effects on tumour initiation and growth. Both HIF-1α and HIF-2α are necessary for the clear cell phenotype. Transcriptomic and proteomic analyses revealed that HIF-1α regulates glycolysis while HIF-2α regulates genes associated with lipoprotein metabolism, ribosome biogenesis and E2F and MYC transcriptional activities. Deficiency of HIF-2α increased CD8+ T cell infiltration and activation. These studies reveal different functions of HIF-1α and HIF-2α in ccRCC. SIGNIFICANCE The roles of HIF-1α and HIF-2α in ccRCC pathogenesis remain unclear. Using a mouse genetic approach we show that HIF-1α but not HIF-2α is important for tumour formation, contrary to predictions from studies of human ccRCC. We show that HIF-1α and HIF-2α transcriptionally regulate different aspects of metabolism and identify HIF-2α as a suppressor of immune cell infiltration and activation.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:08:16.060.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Oliver Schilling
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-12-06 05:20:42	ID requested
1	2020-07-01 21:58:23	announced
⏵ 2	2024-10-22 05:08:16	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

curator keyword: Biological, Biomedical

submitter keyword: mouse model, hypoxia induced factor,renal cancer

Prof. Dr. Oliver Schilling
contact affiliation	Prof. Dr. Oliver Schilling Heisenberg Professor of Translational Proteomics Institute of Surgical Pathology Faculty of Medicine University of Freiburg Breisacher Strasse 115a D-79106 Freiburg, Germany +49 761 27080610 oliver.schilling@mol-med.uni-freiburg.de
contact email	oliver.schilling@mol-med.uni-freiburg.de
lab head
Oliver Schilling
contact affiliation	University of Freiburg
contact email	oliver.schilling@mol-med.uni-freiburg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD016630
     1. Label: PRIDE project
     2. Name: HIF-1α and HIF-2α differently regulate tumour development, metabolism and inflammation of clear cell renal cell carcinoma in mice