SF3B1 mutation in pancreatic cancer contributes to aerobic glycolysis and tumor growth through a PP2A-c-Myc axis.

ABSTRACT: Hot spot gene mutations in splicing factor 3b subunit 1 (SF3B1) are observed in many types of cancer and create abundant aberrant mRNA splicing, which is profoundly implicated in tumorigenesis. Here, we identified that the SF3B1 K700E (SF3B1^K700E ) mutation is strongly associated with tumor growth in pancreatic ductal adenocarcinoma (PDAC). Knockdown of SF3B1 significantly retarded cell proliferation and tumor growth in a cell line (Panc05.04) with the SF3B1^K700E mutation. However, SF3B1 knockdown had no notable effect on cell proliferation in two cell lines (BxPC3 and AsPC1) carrying wild-type SF3B1. Ectopic expression of SF3B1^K700E but not SF3B1^WT in SF3B1-knockout Panc05.04 cells largely restored the inhibitory role induced by SF3B1 knockdown.

SUBMITTER: Yang JY 

PROVIDER: S-EPMC8564647 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature