ABSTRACT
The splicing factor SF3B1 is recurrently mutated in various tumors, including pancreatic ductal adenocarcinoma (PDAC). The impact of the hotspot mutation SF3B1K700E on the PDAC pathogenesis, however, remains elusive. Here, we demonstrate that Sf3b1K700E alone is insufficient to induce malignant transformation of the murine pancreas, but increases aggressiveness of PDAC if it co-occurs together with mutated KRAS and p53. We further demonstrate that SF3B1K700E reduces epithelial–mesenchymal transition (EMT) and confers resistance to TGF-β1-induced cell death, and provide evidence that this phenotype is in part mediated through aberrant splicing of Map3k7. Taken together, our work suggests that SF3B1K700E acts as an oncogenic driver in PDAC through enhancing resistance to the tumor suppressive effects of TGF-β.
Competing Interest Statement
The authors have declared no competing interest.
