SRC enhanced cisplatin resistance in bladder cancer by reprogramming glycolysis and pentose phosphate pathway.

ABSTRACT: The development of cisplatin resistance often results in a grim prognosis in advanced or recurrent bladder cancer. However, effective treatment strategies for cisplatin resistance have not been well established. Herein, we found that overactivation of SRC is associated with cisplatin-resistance. SRC activates hexokinase2 which up-regulates glycolysis and especially the pentose phosphate pathway that leading to increased nucleotide synthesis and NADPH production which can neutralize reactive oxygen species (ROS) induced by cisplatin, thereby protecting bladder cancer cells from cisplatin-induced DNA damage. This phenomenon was effectively reversed by knockout of SRC and inhibition of SRC activity by the SRC inhibitor, eCF506. Moreover, we constructed Cell-derived xenograft (CDX) and Patient

SUBMITTER: Gong Y 

PROVIDER: S-EPMC11724026 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature