TRIP13 protects pancreatic cancer cells against intrinsic and therapy-induced DNA replication stress
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 re-programmed and deployed in diverse ways in different cancers. Mutant KRAS is the driver oncogene in 90% of Pancreatic Ductal Adenocarcinomas. We investigated DDR mechanisms by which KRAS-induced DNA replication stress is tolerated in normal human pancreatic epithelial cells (HPNE). Using a candidate screening approach, we identify TRIP13 as a KRAS-induced mRNA that is also expressed at high levels in PDAC relative to normal tissues. As a part of the project, the KRAS-induced transcriptomic changes were examined in KRAS-transformed HPNE cells.