Role of lactylation in tumorigenesis: Analysis based on the ten hallmarks of cancer

Figure 3 Lactylation in the tumor microenvironment modulates immune and matrix remodeling functions. Elevated lactate levels, catalyzed by lactate dehydrogenase, lead to modifications of transcription factors like signal transducer and activator of transcription 6 and peroxisome proliferator-activated receptor-gamma in tumor-associated macrophages, promoting M2 polarization and the expression of immune-suppressive genes such as interleukin-10 and transforming growth factor-β. This modification inhibits the activity of effector T cells and natural killer cells, enhancing the immunosuppressive environment. Additionally, lactylation of fibroblast cell factors like nuclear factor kappa B cells and activating protein-1 promotes matrix remodeling, increasing cell migration, invasion, and metastasis, thus driving tumor progression through immune evasion and enhanced matrix degradation. NF-κB: Nuclear factor kappa B; PI3K/AKT/mTOR: Phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin; H3K: Histone H3 lysine; HK2: Hexokinase 2.