SF3B1 facilitates HIF1-signaling and promotes malignancy in pancreatic cancer
0301 basic medicine
HIF1 transcription
pancreatic cancer
10050 Institute of Pharmacology and Toxicology
10184 Institute of Veterinary Pathology
610 Medicine & health
hypoxia; glycolysis; HIF1 transcription; splicing; SF3B1; pancreatic cancer; chromophobe renal cell carcinoma
Mice
splicing
03 medical and health sciences
1300 General Biochemistry, Genetics and Molecular Biology
10049 Institute of Pathology and Molecular Pathology
Cell Line, Tumor
Animals
Hypoxia
0303 health sciences
chromophobe renal cell carcinoma
hypoxia
SF3B1
glycolysis
Hypoxia-Inducible Factor 1, alpha Subunit
Phosphoproteins
3. Good health
Pancreatic Neoplasms
Hypoxia-Inducible Factor 1
RNA Splice Sites
RNA Splicing Factors
Signal Transduction
DOI:
10.1016/j.celrep.2022.111266
Publication Date:
2022-08-23T14:36:26Z
AUTHORS (25)
ABSTRACT
ISSN:2211-1247<br/>Cell Reports, 40 (8)<br/>ISSN:2666-3864<br/>Mutations in the splicing factor SF3B1 are frequently occurring in various cancers and drive tumor progression through the activation of cryptic splice sites in multiple genes. Recent studies also demonstrate a positive correlation between the expression levels of wild-type SF3B1 and tumor malignancy. Here, we demonstrate that SF3B1 is a hypoxia-inducible factor (HIF)-1 target gene that positively regulates HIF1 pathway activity. By physically interacting with HIF1α, SF3B1 facilitates binding of the HIF1 complex to hypoxia response elements (HREs) to activate target gene expression. To further validate the relevance of this mechanism for tumor progression, we show that a reduction in SF3B1 levels via monoallelic deletion of Sf3b1 impedes tumor formation and progression via impaired HIF signaling in a mouse model for pancreatic cancer. Our work uncovers an essential role of SF3B1 in HIF1 signaling, thereby providing a potential explanation for the link between high SF3B1 expression and aggressiveness of solid tumors.<br/>
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (45)
CITATIONS (10)
EXTERNAL LINKS
PlumX Metrics
RECOMMENDATIONS
FAIR ASSESSMENT
Coming soon ....
JUPYTER LAB
Coming soon ....