SHMT2 and esophageal cancer: In esophageal cancer, hypoxia stabilizes serine hydroxymethyltransferase 2 (SHMT2) via lactylation, which enhances its interaction with the key enzyme in one-carbon metabolism, methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1-like (MTHFD1L), thereby facilitating a malignant phenotype (Fig. 3b)57.