SF3B1 facilitates HIF1-signaling and promotes malignancy in pancreatic cancer

• DOI: 10.1016/j.celrep.2022.111266
• Publication Date: 2022-08-23T14:36:26Z
• Authors: Patrik Simmler; Cédric Cortijo; Lisa Maria Koch; Patricia Galliker; Silvia Angori; Hella Anna Bolck; Christina Mueller; Ana Vukolic; Peter Mirtschink; Yann Christinat; Natalie R. Davidson; Kjong-Van Lehmann; Giovanni Pellegrini; Chantal Pauli; Daniela Lenggenhager; Ilaria Guccini; Till Ringel; Christian Hirt; Kim Fabiano Marquart; Moritz Schaefer; Gunnar Rätsch; Matthias Peter; Holger Moch; Markus Stoffel; Gerald Schwank
• Keywords: Tumor progression; Hypoxia-Inducible Factors; Splicing factor

Mutations in the splicing factor SF3B1 are frequently occurring various cancers and drive tumor progression through activation of cryptic splice sites multiple genes. Recent studies also demonstrate a positive correlation between expression levels wild-type malignancy. Here, we that is hypoxia-inducible (HIF)-1 target gene positively regulates HIF1 pathway activity. By physically interacting with HIF1α, facilitates binding complex to hypoxia response elements (HREs) activate expression. To further validate relevance this mechanism for progression, show reduction via monoallelic deletion Sf3b1 impedes formation impaired HIF signaling mouse model pancreatic cancer. Our work uncovers an essential role signaling, thereby providing potential explanation link high aggressiveness solid tumors.