Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

SF3B1 promotes glycolysis and tumor malignancy through splicing-independent activation of HIF1α

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE201462 | GEO | 2022/06/22

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

SF3B1 promotes glycolysis and tumor malignancy through splicing-independent activation of HIF1α [ChIP-Seq]

Project description:Splicing factor 3b subunit 1 (SF3B1) is one of the most frequently mutated spliceosomal components in cancer. Recent studies additionally imply an involvement of the wildtype protein in tumor progression, but the underlaying mechanism remains elusive. Here we report that SF3B1 acts as a coactivator for hypoxia-inducible factor (HIF) 1α. SF3B1 directly interacts with HIF1a, augments HIF1a-HIF1b heterodimer binding to hypoxia response elements in vivo and enhances transactivation of HIF target genes. In human patients, primary patient cells and in a mouse model of pancreatic ductal adenocarcinoma (PDAC), efficient HIF1a-signalling relies on SF3B1. Monoallelic deletion of Sf3b1 in this mouse tumor model severely delays tumor initiation and development and diminishes HIF target gene transcription, glucose uptake and proliferation in corresponding tumor organoids in hypoxia, while splicing remains functional. Here, we define a subset of aggressive chromophobe renal cell carcinomas (chRCCs) able to transcriptionally compensate monoallelic SF3B1 loss, a feature that correlates with poor prognosis and lymph node spread and we show that the oncogenic hotspot mutation SF3B1K700E has reduced co-activation efficiency. Also, we report increased sensitivity of cells with low levels of SF3B1 to the HIF-inhibitor PX-478. These findings reveal a splicing-independent, tumor promoting function of SF3B1, important in the pathogenesis of PDAC and other cancers.

2022-06-22 | GSE201461 | GEO

SF3B1 promotes glycolysis and tumor malignancy through splicing-independent activation of HIF1α [RNA-Seq]

2022-06-22 | GSE201427 | GEO

SF3B1 promotes glycolysis and tumor malignancy through splicing-independent activation of HIF1α [RNA-Seq murine organoids]

2022-06-25 | GSE206703 | GEO

SF3B1 promotes glycolysis and tumor malignancy through splicing-independent activation of HIF1α

Project description:SF3B1 promotes glycolysis and tumor malignancy through splicing-independent activation of HIF1α

| PRJNA831827 | ENA

SF3B1 promotes glycolysis and tumor malignancy through splicing-independent activation of HIF1α [RNA-Seq]

Project description:SF3B1 promotes glycolysis and tumor malignancy through splicing-independent activation of HIF1α [RNA-Seq]

| PRJNA831709 | ENA

SF3B1 promotes glycolysis and tumor malignancy through splicing-independent activation of HIF1α [ChIP-Seq]