KRAS G12D mutation eliminates reactive oxygen species through the Nrf2/CSE/H ₂S axis and contributes to pancreatic cancer growth.

ABSTRACT: In pancreatic cancer, KRAS G12D can trigger pancreatic cancer initiation and development. Rapid tumor growth is often accompanied by excess intracellular reactive oxygen species (ROS) production, which is unfavorable to tumor. However, the regulation of intracellular ROS levels in KRAS mutant pancreatic cancer remains unclear. In this study, we establish BxPC3 stable cell strains expressing KRAS wild type (WT) and G12D mutation and find unchanged ROS levels despite higher glycolysis and proliferation viability in KRAS mutant cells than KRAS WT cells. The key hydrogen sulfide (H ₂S)-generating enzyme cystathionine-γ-lyase (CSE) is upregulated in KRAS mutant BxPC3 cells, and its knockdown significantly increases intracellular ROS levels and decreases cell glycolysis and proliferat

SUBMITTER: Fan K 

PROVIDER: S-EPMC9828102 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature