Serine starvation suppresses the progression of esophageal cancer by regulating the synthesis of purine nucleotides and NADPH.

ABSTRACT: Serine metabolism provides important metabolic intermediates that support the rapid proliferation of tumor cells. However, the role of serine metabolism in esophageal squamous cell carcinoma (ESCC) and the underlying mechanism remains unclear. Here, we show that serine starvation predominantly inhibits ESCC cell proliferation by suppressing purine nucleotides and NADPH synthesis. Mechanistically, serine depletion led to the accumulation of aminoimidazole carboxamide ribonucleoside (AICAR), an intermediate metabolite of de novo purine synthesis, and AMP/ATP ratio. These increases activated 5'-AMP-activated kinase (AMPK), which subsequently inhibited the mTORC1 pathway by phosphorylating Raptor at Ser792. Moreover, serine depletion decreased NADPH level followed by elevated reactive oxygen s

SUBMITTER: Jie H 

PROVIDER: S-EPMC11827256 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature