Lactate metabolism and protein lactylation in colorectal cancer: from metabolic reprogramming to epigenetic regulation - PubMed
5 hours ago
- #colorectal-cancer
- #epigenetic-regulation
- #lactate-metabolism
- Colorectal cancer (CRC) undergoes metabolic reprogramming leading to excessive lactate accumulation.
- Lactate remodels the tumor microenvironment, promoting immune suppression, angiogenesis, and therapeutic resistance.
- Lactate serves as a substrate for lysine lactylation (Kla), linking metabolism to epigenetic regulation.
- Key players include glycolytic enzymes, monocarboxylate transporters (MCT1/4-CD147), and Kla writers/erasers/readers.
- A three-step therapeutic framework is proposed: reduce lactate production, block lactate shuttling, and inhibit Kla-mediated transcriptional reprogramming.
- Biomarkers like serum LDH, tissue Kla immunohistochemistry, and hyperpolarized MRI aid in translational feasibility.
- The lactate-lactylation axis offers actionable targets for metabolism-driven precision therapy in microsatellite-stable CRC (MSS CRC).