PGAM1 Inhibition Promotes HCC Ferroptosis and Synergizes with Anti-PD-1 Immunotherapy.

ABSTRACT: The combination of immunotherapy and molecular targeted therapy exhibits promising therapeutic efficacy in hepatocellular carcinoma (HCC), but the underlying mechanism is still unclear. Here, phosphoglycerate mutase 1 (PGAM1) is identified as a novel immunometabolic target by using a bioinformatic algorithm based on multiple HCC datasets. PGAM1 is highly expressed in HCC and associated with a poor prognosis and a poor response to immunotherapy. In vitro and in vivo experiments indicate that targeting PGAM1 inhibited HCC cell growth and promoted the infiltration of CD8⁺ T-cells due to decreased enzymatic activity. Mechanistically, inhibition of PGAM1 promotes HCC cell ferroptosis by downregulating Lipocalin (LCN2) by inducing energy stress and ROS-dependent AKT inhibition, which

SUBMITTER: Zheng Y 

PROVIDER: S-EPMC10582428 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature