Palmitic acid-induced endoplasmic reticulum stress links metabolic stress to senescence and regulates cell fate via PERK signalling in colon cancer cells

Palmitic acid promotes cancer progression and induces endoplasmic reticulum stress, which is associated with a misfolded/unfolded protein response. The study aims to explore the impact of metabolic-stress induced by palmitic acid on cell fate decisions in colon cancer cell HCT15, with a specific focus on PERK signalling that connects metabolic-stress to senescence. Palmitic acid-induced oxidative stress is evidenced by increased ROS production, elevated MDA levels, and alterations in antioxidant activities. Bioinformatics analysis of GEO datasets on senescence in HCT15 cells revealed a PERK-mediated pathway, supporting a link between palmitic acid-induced metabolic stress and senescence. This study emphasises the critical role of palmitic acid-induced ER stress in connecting metabolic stress to senescence in colon cancer cells and the involvement of PERK signalling as a key mediator in this process. These insights provide a deeper understanding of how metabolic stress contributes to senescence, potentially revealing new therapeutic targets for managing colon cancer progression.