TRIP13 protects pancreatic cancer cells against intrinsic and therapy-induced DNA replication stress.

ABSTRACT: Oncogene activation in normal untransformed cells induces DNA replication stress and creates a dependency on DNA damage response (DDR) mechanisms for cell survival. Different oncogenic stimuli signal via distinct mechanisms in every cancer setting. The DDR is also pathologically reprogrammed and deployed in diverse ways in different cancers. Because mutant KRAS is the driver oncogene in 90% of pancreatic ductal adenocarcinomas (PDACs), here we have investigated DDR mechanisms by which KRAS-induced DNA replication stress is tolerated in normal human pancreatic epithelial cells [human pancreatic nestin-expressing (HPNE) cells]. Using a candidate screening approach, we identify TRIP13 as a KRAS^G12V-induced messenger RNA that is also expressed at high levels in PDAC relative to norm

SUBMITTER: Anand JR 

PROVIDER: S-EPMC11923746 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature