Oxaliplatin resistance in colorectal cancer enhances TRAIL sensitivity via death receptor 4 upregulation and lipid raft localization

Colorectal cancer (CRC) remains a leading cause of death, and its mortality is associated with metastasis chemoresistance. We demonstrate that oxaliplatin-resistant CRC cells are sensitized to TRAIL-mediated apoptosis. Oxaliplatin-resistant exhibited transcriptional downregulation caspase-10, but this had minimal effects on TRAIL sensitivity following CRISPR-Cas9 deletion caspase-10 in parental cells. Sensitization were found be result increased DR4, as well significantly enhanced DR4 palmitoylation translocation into lipid rafts. Raft perturbation via nystatin resveratrol altered DR4/raft colocalization sensitivity. Blood samples from metastatic patients treated liposomes, 57% reduction viable circulating tumor (CTCs) was observed. Increased DR4/lipid raft CTCs correspond oxaliplatin resistance efficacy liposomes. To our knowledge, the first study investigate role rafts primary CTCs.