Lactate-driven lysine lactylation in tumor progression, therapy resistance, and prognosis

Dan Huang , Lan Jiang , Qihui Zhao , Zhe Chen

MedScience ››

PDF (638KB)
MedScience ›› DOI: 10.1007/s11684-026-1212-4
COMMENT
Lactate-driven lysine lactylation in tumor progression, therapy resistance, and prognosis
Author information +
History +
PDF (638KB)

Cite this article

Download citation ▾
Dan Huang, Lan Jiang, Qihui Zhao, Zhe Chen. Lactate-driven lysine lactylation in tumor progression, therapy resistance, and prognosis. MedScience DOI:10.1007/s11684-026-1212-4

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Zhu R , Ye X , Lu X , Xiao L , Yuan M , Zhao H , Guo D , Meng Y , Han H , Luo S , Wu Q , Jiang X , Xu J , Tang Z , Tao YJ , Lu Z . ACSS2 acts as a lactyl-CoA synthetase and couples KAT2A to function as a lactyltransferase for histone lactylation and tumor immune evasion. Cell Metab 2025; 37(2): 361–376.e7

[2]

Chen H , Li Y , Li H , Chen X , Fu H , Mao D , Chen W , Lan L , Wang C , Hu K , Li J , Zhu C , Evans I , Cheung E , Lu D , He Y , Behrens A , Yin D , Zhang C . NBS1 lactylation is required for efficient DNA repair and chemotherapy resistance. Nature 2024; 631(8021): 663–669

[3]

Chen Y , Wu J , Zhai L , Zhang T , Yin H , Gao H , Zhao F , Wang Z , Yang X , Jin M , Huang B , Ding X , Li R , Yang J , He Y , Wang Q , Wang W , Kloeber JA , Li Y , Hao B , Zhang Y , Wang J , Tan M , Li K , Wang P , Lou Z , Yuan J . Metabolic regulation of homologous recombination repair by MRE11 lactylation. Cell 2024; 187(2): 294–311.e21

[4]

Li F , Si W , Xia L , Yin D , Wei T , Tao M , Cui X , Yang J , Hong T , Wei R . Positive feedback regulation between glycolysis and histone lactylation drives oncogenesis in pancreatic ductal adenocarcinoma. Mol Cancer 2024; 23(1): 90

[5]

Luo Y , Yang Z , Yu Y , Zhang P . HIF1α lactylation enhances KIAA1199 transcription to promote angiogenesis and vasculogenic mimicry in prostate cancer. Int J Biol Macromol 2022; 222(Pt B): 2225–2243

[6]

Hong H , Chen X , Wang H , Gu X , Yuan Y , Zhang Z . Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma. Proteomics 2023; 23(9): e2200432

[7]

Fan H , Wang L , Zeng X , Xiong C , Yu D , Zhang X , Chen J , Meng Z , Campbell A , Huang W , Mei H , Sun H . Redox-inducible radiomimetic photosensitizers selectively suppress cancer cell proliferation by damaging DNA through radical cation chemistry. Angew Chem Int Ed Engl 2025; 64(1): e202413352

[8]

Li G , Wang D , Zhai Y , Pan C , Zhang J , Wang C , Huang R , Yu M , Li Y , Liu X , Liu Y , Wu F , Zhao Z , Hu H , Shi Z , Kahlert UD , Jiang T , Zhang W . Glycometabolic reprogramming-induced XRCC1 lactylation confers therapeutic resistance in ALDH1A3-overexpressing glioblastoma. Cell Metab 2024; 36(8): 1696–1710.e10

[9]

Yang Z , Yan C , Ma J , Peng P , Ren X , Cai S , Shen X , Wu Y , Zhang S , Wang X , Qiu S , Zhou J , Fan J , Huang H , Gao Q . Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma. Nat Metab 2023; 5(1): 61–79

[10]

Chao J , Chen GD , Huang ST , Gu H , Liu YY , Luo Y , Lin Z , Chen ZZ , Li X , Zhang B , Xu X , He S . High histone H3K18 lactylation level is correlated with poor prognosis in epithelial ovarian cancer. Neoplasma 2024; 71(4): 319–332

[11]

Zhang D , Tang Z , Huang H , Zhou G , Cui C , Weng Y , Liu W , Kim S , Lee S , Perez-Neut M , Ding J , Czyz D , Hu R , Ye Z , He M , Zheng YG , Shuman HA , Dai L , Ren B , Roeder RG , Becker L , Zhao Y . Metabolic regulation of gene expression by histone lactylation. Nature 2019; 574(7779): 575–580

[12]

Gao J , Liu R , Huang K , Li Z , Sheng X , Chakraborty K , Han C , Zhang D , Becker L , Zhao Y . Dynamic investigation of hypoxia-induced L-lactylation. Proc Natl Acad Sci USA 2025; 122(10): e2404899122

[13]

Gou Z , Sun Q , Li J . Exploring lactylation and cancer biology: insights from pathogenesis to clinical applications. Front Cell Dev Biol 2025; 13: 1598232

[14]

Sgarra R , Battista S , Cerchia L , Manfioletti G , Fedele M . Mechanism of action of lactic acid on histones in cancer. Antioxid Redox Signal 2024; 40(4–6): 236–249

[15]

Jambhekar A , Dhall A , Shi Y . Roles and regulation of histone methylation in animal development. Nat Rev Mol Cell Biol 2019; 20(10): 625–641

[16]

Li H , Sun L , Gao P , Hu H . Lactylation in cancer: current understanding and challenges. Cancer Cell 2024; 42(11): 1803–1807

[17]

Zhu W , Fan C , Hou Y , Zhang Y . Lactylation in tumor microenvironment and immunotherapy resistance: new mechanisms and challenges. Cancer Lett 2025; 627: 217835

[18]

Tan Q , Liu M , Tao X . Targeting lactylation: from metabolic reprogramming to precision therapeutics in liver diseases. Biomolecules 2025; 15(8): 1178

RIGHTS & PERMISSIONS

Higher Education Press

PDF (638KB)

389

Accesses

0

Citation

Detail

Sections
Recommended

/