Lactylation as a metabolic-epigenetic switch in cancer: dual roles in cell death resistance and therapeutic vulnerability - PubMed
3 days ago
- #lactylation
- #epigenetics
- #cancer
- Protein lactylation acts as a metabolic-epigenetic switch in cancer, influencing treatment resistance and therapeutic vulnerability.
- Key enzymatic pathways (AARS1/2, KATs, HDACs) and non-enzymatic mechanisms (MGO/LGSH) regulate lactylation.
- Lactylation modifies non-histone proteins (e.g., p53, XLF) and interacts with other PTMs, such as H3K18la and H3K27ac in T-ALL.
- Lactylation enhances intrinsic (e.g., DNA repair via BLM K24la) and extrinsic resistance (e.g., PD-L1 upregulation).
- Targeting lactylation (e.g., LDHA inhibition, KAT inhibitors) shows synergistic effects in sensitizing tumors to therapy.
- Future directions include enzyme-substrate specificity studies, drug design, and lactylomic biomarkers for precision oncology.