NPR1 Promotes Lipid Droplet Lipolysis to Enhance Mitochondrial Oxidative Phosphorylation and Fuel Gastric Cancer Metastasis.

ABSTRACT: Metabolic reprogramming driven by oncogenes plays a critical role in promoting and sustaining multiple steps of gastric cancer metastasis. However, the key metabolic driver of metastasis that can lead to the development of targeted therapies for preventing and treating metastatic gastric cancer remains elusive. Here, it is identified that the transmembrane guanylate cyclase, natriuretic peptide receptor 1 (NPR1), promoted gastric cancer lymph node metastasis by activating lipid droplet lipolysis and enhancing mitochondrial oxidative phosphorylation (OXPHOS). Clinical analysis reveals that elevated NPR1 protein level is correlated with increased lymph node metastasis and shorter patient survival. Functionally, NPR1 induced lipolysis of stored lipid droplets, releasing bioavailable fatty aci

SUBMITTER: Fu H 

PROVIDER: S-EPMC12499470 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature