Histone Lactylation in Cancer: Linking Hypoxia-Driven Metabolism to Epigenetic Regulation
PDF (angielski)

Słowa kluczowe

Histone lactylation
lysine lactylation
epigenetics
cancer
hypoxia
lactate
tumor microenvironment

Jak cytować

Ostapowicz, Julia, i Katarzyna Kulcenty. 2026. „Histone Lactylation in Cancer: Linking Hypoxia-Driven Metabolism to Epigenetic Regulation”. Zeszyty Naukowe WCO 23 (3). https://doi.org/10.21641/los.2026.23.3.306.

Abstrakt

Solid tumors are frequently characterized by hypoxia, which drives metabolic reprogramming toward glycolysis and increased lactate production. Beyond its role as a metabolic end product, lactate can influence gene regulation through histone lactylation, a recently identified post-translational modification linking cellular metabolism with epigenetic regulation. In cancer, hypoxia-associated lactate accumulation and histone lactylation have been implicated in tumor proliferation, invasion, epithelial–mesenchymal transition, immune modulation, and therapeutic resistance. This review summarizes current knowledge of the relationship between hypoxia, lactate metabolism, and histone lactylation, focusing on the molecular mechanisms regulating this modification and its potential role in cancer progression. We also discuss current methodological challenges and the potential of the lactate–histone lactylation axis as a target for future diagnostic and therapeutic strategies in oncology.

PDF (angielski)

Bibliografia

1. Yu X, Zhao H, Wang R, Chen Y, Ouyang X, Li W, et al. Cancer epigenetics: from laboratory studies and clinical trials to precision medicine. Cell Death Discov. 2024;10(1):28.

2. Almalki AA. The role of epigenetics in cancer: From pathways to the clinic. J Family Med Prim Care. 2025;14(8):3104-14.

3. Yu X, Yang J, Xu J, Pan H, Wang W, Yu X, et al. Histone lactylation: from tumor lactate metabolism to epigenetic regulation. Int J Biol Sci. 2024;20(5):1833-54.

4. Zhang D, Tang Z, Huang H, Zhou G, Cui C, Weng Y, et al. Metabolic regulation of gene expression by histone lactylation. Nature. 2019;574(7779):575-80.

5. Chen Z, Han F, Du Y, Shi H, Zhou W. Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions. Signal Transduct Target Ther. 2023;8(1):70.

6. Ostapowicz J, Ostrowska K, Golusinski W, Kulcenty K, Suchorska WM. Improving therapeutic strategies for Head and Neck Cancer: Insights from 3D hypoxic cell culture models in treatment response evaluation. Adv Med Sci. 2024;69(2):368-76.

7. Debbi K, Loganadane G, To N, Cherif MA, Boukhobza C, Rida H, et al. New approaches to overcome radioresistance in glioblastoma: mechanisms, targets and role of innovative therapies, new particles and non-photon radiotherapy in 2024. A systematic review. Rep Pract Oncol Radiother. 2025;30(2):269-81.

8. Basheeruddin M, Qausain S. Hypoxia-Inducible Factor 1-Alpha (HIF-1alpha): An Essential Regulator in Cellular Metabolic Control. Cureus. 2024;16(7):e63852.

9. Ran J, Li F, Zhan L, Jin Y, Dong Q, Li X, et al. Hypoxia regulates glycolysis through the HIF-1alpha/BMAL1/ALDOC axis to reduce oxaliplatin sensitivity in colorectal cancer. J Cancer. 2025;16(8):2503-15.

10. Sureka N, Maheshwari R, Agravat A, Singhal S, Zaman S, Rishi B, et al. Hypoxic microenvironment in cancer: role in metabolic reprogramming. Front Oncol. 2026;16:1771365.

11. Chowdhury M, Das PK. Hypoxia: Intriguing Feature in Cancer Cell Biology. ChemMedChem. 2024;19(9):e202300551.

12. Ivashkiv LB. The hypoxia-lactate axis tempers inflammation. Nat Rev Immunol. 2020;20(2):85-6.

13. Peng X, Du J. Histone and non-histone lactylation: molecular mechanisms, biological functions, diseases, and therapeutic targets. Mol Biomed. 2025;6(1):38.

14. He Y, Song T, Ning J, Wang Z, Yin Z, Jiang P, et al. Lactylation in cancer: Mechanisms in tumour biology and therapeutic potentials. Clin Transl Med. 2024;14(11):e70070.

15. Xie B, Zhang M, Li J, Cui J, Zhang P, Liu F, et al. KAT8-catalyzed lactylation promotes eEF1A2-mediated protein synthesis and colorectal carcinogenesis. Proc Natl Acad Sci U S A. 2024;121(8):e2314128121.

16. Zhang D, Jiang M, Li P, Laster KV, Zhao D, Zhi Y, et al. CHI-KAT8i5 suppresses ESCC tumor growth by inhibiting KAT8-mediated c-Myc stability. Cell Rep. 2025;44(1):115135.

17. Jia Z, Lu S, Wang Z, Ge P. From mechanism to targeted therapy: Advances in histone lactylation-driven cancer progression (Review). Oncol Lett. 2026;31(1):28.

18. Visan I. Histone lactylation. Nat Immunol. 2019;20(12):1558.

19. Zang Y, Wang A, Zhang J, Xia M, Jiang Z, Jia B, et al. Hypoxia promotes histone H3K9 lactylation to enhance LAMC2 transcription in esophageal squamous cell carcinoma. iScience. 2024;27(7):110188.

20. Yu J, Chai P, Xie M, Ge S, Ruan J, Fan X, et al. Histone lactylation drives oncogenesis by facilitating m(6)A reader protein YTHDF2 expression in ocular melanoma. Genome Biol. 2021;22(1):85.

21. Wang D, Du G, Chen X, Wang J, Liu K, Zhao H, et al. Zeb1-controlled metabolic plasticity enables remodeling of chromatin accessibility in the development of neuroendocrine prostate cancer. Cell Death Differ. 2024;31(6):779-91.

22. Nguyen NTB, Gevers S, Kok RNU, Burgering LM, Neikes H, Akkerman N, et al. Lactate controls cancer stemness and plasticity through epigenetic regulation. Cell Metab. 2025;37(4):903-19 e10.

23. Zhao F, Tang Q, Liu J. Functional impacts of lactylation in Hypoxia‒primed mesenchymal stromal cells. Front Cell Dev Biol. 2025;13:1678282.

24. Zhang Y, Song H, Li M, Lu P. Histone lactylation bridges metabolic reprogramming and epigenetic rewiring in driving carcinogenesis: Oncometabolite fuels oncogenic transcription. Clin Transl Med. 2024;14(3):e1614.

25. Bao C, Ma Q, Ying X, Wang F, Hou Y, Wang D, et al. Histone lactylation in macrophage biology and disease: from plasticity regulation to therapeutic implications. EBioMedicine. 2025;111:105502.

26. Zhang D, Gao J, Zhu Z, Mao Q, Xu Z, Singh PK, et al. Lysine L-lactylation is the dominant lactylation isomer induced by glycolysis. Nat Chem Biol. 2025;21(1):91-9.

Creative Commons License

Utwór dostępny jest na licencji Creative Commons Uznanie autorstwa – Bez utworów zależnych 4.0 Międzynarodowe.

Prawa autorskie (c) 2026 Zeszyty Naukowe WCO

Downloads

Download data is not yet available.