Upregulated FSP1 by GPD1/1L mediated lipid droplet accumulation enhances ferroptosis resistance and peritoneal metastasis in gastric cancer.

ABSTRACT: To successfully metastasize, cancer cells must evade detachment induced cell death, known as anoikis. Unraveling the mechanisms that gastric cancer (GC) circumvent anoikis and achieve peritoneal metastasis especially during unanchored growth, could significantly improve patient outcomes. Our study reveals that GC cells exhibit increased lipid peroxidation, MDA production, and cell death during suspension culture, which can be mitigated by the intervention with liproxstatin-1 and ferrostatin-1. We discovered that oleic acid (OA) or adipocytes stimulate lipid accumulation in GC cells, thereby inhibiting lipid peroxidation and cell death. Lipid mass spectrometry confirmed an upregulation of triglyceride synthesis, indicating that the accumulation of lipid droplet may confer resistance to ferr

SUBMITTER: Lin G 

PROVIDER: S-EPMC11899195 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature