Phosphoglycerate mutase 1 (PGAM1) is a pivotal glycolytic enzyme. It catalyzes the reciprocal conversion between 2-phosphoglycerate and 3-phosphoglycerate. Besides, it stimulates anabolic pathways, generates adenosine triphosphate, and maintains redox balance under hypoxic conditions [3]. As a key enzyme in cancer metabolism, its activity can also divert metabolic reactions from glycolysis into shunts to support macromolecule biosynthesis for cell proliferation [4].

In hepatocellular carcinoma (HCC), inhibition of PGAM1 promotes ferroptosis by downregulating Lipocalin (LCN2) through inducing energy stress and ROS-dependent AKT inhibition, and also increases CD8+ T-cell infiltration due to decreased enzymatic activity, enhancing the efficacy of anti-PD-1 immunotherapy [1]. In prostate cancer, exosomal PGAM1 promotes angiogenesis and metastasis by interacting with ACTG1 [2]. In breast cancer, knockdown of PGAM1 suppresses cell proliferation, invasion, migration, and epithelial-mesenchymal transition, and PGAM1 negatively regulates argininosuccinate synthase 1 (ASS1) expression through the cAMP/AMPK/CEBPB axis [5]. In triple-negative breast cancer, PGAM1 inhibition synergizes with anti-PD-1 immunotherapy, remodeling the tumor microenvironment by increasing antitumor immunocytes and reducing immunosuppressive cell infiltration [6]. In ovarian cancer, PGAM1 promotes glycolytic metabolism and paclitaxel resistance via pyruvic acid production [7].

In conclusion, PGAM1 is a crucial enzyme in glycolysis and cancer-related metabolic reprogramming. Studies on PGAM1 using in vivo models have revealed its significant roles in multiple cancers, including HCC, prostate, breast, triple-negative breast, and ovarian cancers. Targeting PGAM1 may provide new strategies for cancer treatment, especially in combination with immunotherapy [1,2,5,6,7].