EGF/APOC1/CPT1A Axis: A Novel Pathway in Gastric Cancer Metabolism and Therapeutic Targeting

Gastric cancer (GC) relies heavily on the reprogramming of lipid metabolism for energy, growth, and survival. Apolipoprotein C-I (APOC1) is implicated in the reprogramming of lipid metabolic processes in GC, yet the precise molecular mechanisms underlying this association remain incompletely understood. In this study, we identified APOC1 as a key player in GC metabolism and progression. Our findings show that APOC1 is upregulated in GC tissues and cells compared with controls and is correlated with poor prognosis. Furthermore, the overexpression of APOC1 promoted proliferation and migration, whereas the silencing of APOC1 led to decreased tumor growth and metastasis. Moreover, APOC1 was found to augment fatty acid oxidation (FAO) through its interaction with and regulation of carnitine palmitoyltransferase 1A (CPT1A). Disruption of APOC1 resulted in metabolic dysregulation, leading to mitochondrial oxidative stress. Conversely, the upregulation of APOC1 in GC cells promoted the catabolism of long-chain fatty acids, thereby facilitating tumor growth and migration. Mechanistically, APOC1 was shown to be regulated by epidermal growth factor (EGF), and its expression was directly targeted at the transcriptional level by AP-2α binding to its promoter region. Our research reveals a novel association between APOC1 and lipid metabolism, highlighting the EGF/APOC1/CPT1A axis as crucial factors in the progression of GC and potential targets for therapeutic interventions.