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Review Open Access

Impact of lactylation on the pathogenesis of cancer and its clinical application potential (Review)

  • Authors:
    • Xiaomei Wang
    • Jiaqing Chen
    • Bing Wang
    • Yanping Li
    • Xinyue Zhou
    • Yingqiu Song
    • Chenggui Miao
    • Yurong Huang
  • View Affiliations / Copyright

    Affiliations: Department of Nursing Management and Education, School of Nursing, Anhui University of Chinese Medicine, Hefei, Anhui 230012, P.R. China, Department of Pharmacology, School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, Anhui 230012, P.R. China, Department of Respiratory Medicine, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 336
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    Published online on: October 1, 2025
       https://doi.org/10.3892/mmr.2025.13702
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Abstract

Dysregulation of lactate metabolism is a hallmark of multiple pathologies, including cancer, which coordinates metabolic reprogramming and malignant progression. Lactylation, a lactate‑derived post‑translational modification, is a key regulator of tumor cell adaptation, aggressive behavior and immune escape. This modification mechanism links lactate accumulation to carcinogenic signaling and epigenetic dysregulation, providing novel insights into cancer pathogenesis. The present review summarizes the roles of lactylation in tumor microenvironment (TME) remodeling, therapeutic resistance and immunomodulation, and outlines the challenges to clinical translation. Lactate drives the lactylation of histone and non‑histone proteins, and alters chromatin structure and transcriptional programs to maintain tumorigenesis. In the TME, lactylation modulates the phenotypes of stromal cells (such as cancer‑associated fibroblasts) and immune cells (including macrophages and T cells), forming an immunosuppressive niche. Lactylation can also polarize macrophages towards a tumor‑promoting state, inhibit CD8+ T cells and upregulate immune checkpoints. Clinically, lactylation is associated with chemotherapy resistance (such as paclitaxel in breast cancer) and a poor prognosis, highlighting its usefulness as a biomarker. Notably, therapeutic strategies targeting lactate synthesis (such as lactate dehydrogenase A inhibitors), lactate transport (for example, monocarboxylate transporter 1/4 blockers) or lactase (such as histone lactate transferase) have shown promise in preclinical models. In conclusion, lactylation promotes tumor progression while also providing a viable therapeutic target. Deciphering its environment‑dependent mechanisms, particularly its interactions with immune checkpoints and metabolic vulnerabilities, may advance precision oncology. Validating biomarkers and therapies centered on lactylation is a key frontier in improving clinical outcomes.
View Figures

Figure 1

Lactylation, as a post-translational
modification, serves an important role in the occurrence and
development of tumors, provides a new potential target for tumor
therapy, and provides a new perspective for understanding the
mechanism of tumor metabolism and immune escape. The proteins in
green boxes indicate lactylation-related proteins. AML, acute
myeloid leukemia; ATC, anaplastic thyroid cancer; BCa, bladder
cancer; ccRCC, clear cell renal cell carcinoma; CRC, colorectal
cancer; EC, esophageal cancer; GBM, glioblastoma; GC, gastric
cancer; HCC, hepatocellular carcinoma; iCCA, intrahepatic
cholangiocarcinoma; LUAD, lung adenocarcinoma; LUSC, lung squamous
cell carcinoma; mCRPC, metastatic castration-resistant PCa; NEPC,
neuroendocrine PCa; NSCLC, non-small cell lung cancer; PML,
promyelocytic leukemia; OC, ovarian cancer; OSCC, oral squamous
cell carcinoma; PCa, prostate cancer; PAAD, pancreatic
adenocarcinoma; PC, pancreatic cancer; PDAC, pancreatic ductal
adenocarcinoma; UM, uveal melanoma.

Figure 2

Mechanism of lactylation in tumor
therapy mainly involves inhibition of tumor cell proliferation,
enhancing the immune system recognition and clearance of tumor
cells, inhibiting tumor angiogenesis and modulating the tumor
microenvironment. Lactylation inhibitors can also be combined with
drug therapy and chemotherapy to enhance the efficacy of
chemotherapy drugs and improve the chemotherapeutic sensitivity of
tumor cells. CCN, cyclin; GBM, glioblastoma; HCC, hepatocellular
carcinoma; HIF-1α, hypoxia-inducible factor-1α; LDH, lactate
dehydrogenase; NSCLC, non-small cell lung cancer; PCa, prostate
cancer; PKM2, pyruvate kinase M2; SLC2A1, solute carrier family 2
member 1; TCA, tricarboxylic acid; Treg, regulatory T.

Figure 3

Tumor cells produce lactate through
glycolysis, resulting in local acidification, further affecting
tumor growth and spread. As a signaling molecule, lactate regulates
tumor growth, invasion, metastasis and therapeutic response.
Lactylation participates in various activities, affects the
function of various immune cells in the tumor microenvironment and
regulates the biological behavior of tumors. α-KG, α-ketoglutarate;
DC, dendritic cell; GLUD, glutamate dehydrogenase; HDAC, histone
deacetylase; Kla, lysine lactylation; LDHA, lactate dehydrogenase
A; NK, natural killer; PDH, pyruvate dehydrogenase; PPP, pentose
phosphate pathway; TCA, tricarboxylic acid; TAM, tumor-associated
macrophage; Treg, regulatory T.
View References

1 

Zhu W, Fan C, Hou Y and Zhang Y: Lactylation in tumor microenvironment and immunotherapy resistance: New mechanisms and challenges. Cancer Lett. 627:2178352025. View Article : Google Scholar

2 

Brooks GA, Curl CC, Leija RG, Osmond AD, Duong JJ and Arevalo JA: Tracing the lactate shuttle to the mitochondrial reticulum. Exp Mol Med. 54:1332–1347. 2022. View Article : Google Scholar : PubMed/NCBI

3 

Fan H, Yang F, Xiao Z, Luo H, Chen H, Chen Z, Liu Q and Xiao Y: Lactylation: Novel epigenetic regulatory and therapeutic opportunities. Am J Physiol Endocrinol Metab. 324:E330–E338. 2023. View Article : Google Scholar : PubMed/NCBI

4 

Lv X, Lv Y and Dai X: Lactate, histone lactylation and cancer hallmarks. Expert Rev Mol Med. 25:e72023. View Article : Google Scholar : PubMed/NCBI

5 

Chen L, Huang L, Gu Y, Cang W, Sun P and Xiang Y: Lactate-lactylation hands between metabolic reprogramming and immunosuppression. Int J Mol Sci. 23:119432022. View Article : Google Scholar

6 

Li S, Dong L and Wang K: Current and future perspectives of lysine lactylation in cancer. Trends Cell Biol. 35:190–193. 2025. View Article : Google Scholar

7 

Yu X, Yang J, Xu J, Pan H, Wang W, Yu X and Shi S: Histone lactylation: From tumor lactate metabolism to epigenetic regulation. Int J Biol Sci. 20:1833–1854. 2024. View Article : Google Scholar

8 

Zhang D, Tang Z, Huang H, Zhou G, Cui C, Weng Y, Liu W, Kim S, Lee S, Perez-Neut M, et al: Metabolic regulation of gene expression by histone lactylation. Nature. 574:575–580. 2019. View Article : Google Scholar : PubMed/NCBI

9 

Irizarry-Caro RA, McDaniel MM, Overcast GR, Jain VG, Troutman TD and Pasare C: TLR signaling adapter BCAP regulates inflammatory to reparatory macrophage transition by promoting histone lactylation. Proc Natl Acad Sci USA. 117:30628–30638. 2020. View Article : Google Scholar : PubMed/NCBI

10 

Wang J, Yang P, Yu T, Gao M, Liu D, Zhang J, Lu C, Chen X, Zhang X and Liu Y: Lactylation of PKM2 suppresses inflammatory metabolic adaptation in pro-inflammatory macrophages. Int J Biol Sci. 18:6210–6225. 2022. View Article : Google Scholar

11 

Hua Q, Mi B, Xu F, Wen J, Zhao L, Liu J and Huang G: Hypoxia-induced lncRNA-AC020978 promotes proliferation and glycolytic metabolism of non-small cell lung cancer by regulating PKM2/HIF-1α axis. Theranostics. 10:4762–4778. 2020. View Article : Google Scholar : PubMed/NCBI

12 

Apostolova P and Pearce EL: Lactic acid and lactate: Revisiting the physiological roles in the tumor microenvironment. Trends Immunol. 43:969–977. 2022. View Article : Google Scholar

13 

Wu Z, Wu H, Dai Y, Wang Z, Han H, Shen Y, Zhang R and Wang X: A pan-cancer multi-omics analysis of lactylation genes associated with tumor microenvironment and cancer development. Heliyon. 10:e274652024. View Article : Google Scholar : PubMed/NCBI

14 

Zhang X, Li Y and Chen Y: Development of a comprehensive gene signature linking hypoxia, glycolysis, lactylation, and metabolomic insights in gastric cancer through the integration of bulk and single-cell RNA-Seq data. Biomedicines. 11:29482023. View Article : Google Scholar : PubMed/NCBI

15 

Huang H, Chen K, Zhu Y, Hu Z, Wang Y, Chen J, Li Y, Li D and Wei P: A multi-dimensional approach to unravel the intricacies of lactylation related signature for prognostic and therapeutic insight in colorectal cancer. J Transl Med. 22:2112024. View Article : Google Scholar : PubMed/NCBI

16 

Sun Y, Wang H, Cui Z, Yu T, Song Y, Gao H, Tang R, Wang X, Li B, Li W and Wang Z: Lactylation in cancer progression and drug resistance. Drug Resist Updat. 81:1012482025. View Article : Google Scholar

17 

Zeng Y, Yu T, Lou Z, Chen L, Pan L and Ruan B: Emerging function of main RNA methylation modifications in the immune microenvironment of digestive system tumors. Pathol Res Pract. 256:1552682024. View Article : Google Scholar

18 

Yang Z, Yan C, Ma J, Peng P, Ren X, Cai S, Shen X, Wu Y, Zhang S, Wang X, et al: Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma. Nat Metab. 5:61–79. 2023. View Article : Google Scholar : PubMed/NCBI

19 

Yang H, Zou X, Yang S, Zhang A, Li N and Ma Z: Identification of lactylation related model to predict prognostic, tumor infiltrating immunocytes and response of immunotherapy in gastric cancer. Front Immunol. 14:11499892023. View Article : Google Scholar

20 

Mao Y, Zhang J, Zhou Q, He X, Zheng Z, Wei Y, Zhou K, Lin Y, Yu H, Zhang H, et al: Hypoxia induces mitochondrial protein lactylation to limit oxidative phosphorylation. Cell Res. 34:13–30. 2024. View Article : Google Scholar : PubMed/NCBI

21 

Zong Z, Xie F, Wang S, Wu X, Zhang Z, Yang B and Zhou F: Alanyl-tRNA synthetase, AARS1, is a lactate sensor and lactyltransferase that lactylates p53 and contributes to tumorigenesis. Cell. 187:2375–2392.e33. 2024. View Article : Google Scholar

22 

Ju J, Zhang H, Lin M, Yan Z, An L, Cao Z, Geng D, Yue J, Tang Y, Tian L, et al: The alanyl-tRNA synthetase AARS1 moonlights as a lactyltransferase to promote YAP signaling in gastric cancer. J Clin Invest. 134:e1745872024. View Article : Google Scholar

23 

Zhou J, Xu W, Wu Y, Wang M, Zhang N, Wang L, Feng Y, Zhang T, Wang L and Mao A: GPR37 promotes colorectal cancer liver metastases by enhancing the glycolysis and histone lactylation via Hippo pathway. Oncogene. 42:3319–3330. 2023. View Article : Google Scholar : PubMed/NCBI

24 

Miao Z, Zhao X and Liu X: Hypoxia induced β-catenin lactylation promotes the cell proliferation and stemness of colorectal cancer through the wnt signaling pathway. Exp Cell Res. 422:1134392023. View Article : Google Scholar : PubMed/NCBI

25 

Yang L, Niu K, Wang J, Shen W, Jiang R, Liu L, Song W, Wang X, Zhang X, Zhang R, et al: Nucleolin lactylation contributes to intrahepatic cholangiocarcinoma pathogenesis via RNA splicing regulation of MADD. J Hepatol. 81:651–666. 2024. View Article : Google Scholar

26 

Song F, Hou C, Huang Y, Liang J, Cai H, Tian G, Jiang Y, Wang Z and Hou J: Lactylome analyses suggest systematic lysine-lactylated substrates in oral squamous cell carcinoma under normoxia and hypoxia. Cell Signal. 120:1112282024. View Article : Google Scholar

27 

Wang M, He T, Meng D, Lv W, Ye J, Cheng L and Hu J: BZW2 modulates lung adenocarcinoma progression through glycolysis-mediated IDH3G lactylation modification. J Proteome Res. 22:3854–3865. 2023. View Article : Google Scholar : PubMed/NCBI

28 

Xie B, Lin J, Chen X, Zhou X, Zhang Y, Fan M, Xiang J, He N, Hu Z and Wang F: CircXRN2 suppresses tumor progression driven by histone lactylation through activating the Hippo pathway in human bladder cancer. Mol Cancer. 22:1512023. View Article : Google Scholar : PubMed/NCBI

29 

Wang R, Xu F, Yang Z, Cao J, Hu L and She Y: The mechanism of PFK-1 in the occurrence and development of bladder cancer by regulating ZEB1 lactylation. BMC Urol. 24:592024. View Article : Google Scholar

30 

Wang D, Du G, Chen X, Wang J, Liu K, Zhao H, Cheng C, He Y, Jing N, Xu P, et al: Zeb1-controlled metabolic plasticity enables remodeling of chromatin accessibility in the development of neuroendocrine prostate cancer. Cell Death Differ. 31:779–791. 2024. View Article : Google Scholar : PubMed/NCBI

31 

Pandkar MR, Sinha S, Samaiya A and Shukla S: Oncometabolite lactate enhances breast cancer progression by orchestrating histone lactylation-dependent c-Myc expression. Transl Oncol. 37:1017582023. View Article : Google Scholar

32 

Hou X, Ouyang J, Tang L, Wu P, Deng X, Yan Q, Shi L, Fan S, Fan C, Guo C, et al: KCNK1 promotes proliferation and metastasis of breast cancer cells by activating lactate dehydrogenase A (LDHA) and up-regulating H3K18 lactylation. PLoS Biol. 22:e30026662024. View Article : Google Scholar

33 

He Y, Ji Z, Gong Y, Fan L, Xu P, Chen X, Miao J, Zhang K, Zhang W, Ma P, et al: Numb/Parkin-directed mitochondrial fitness governs cancer cell fate via metabolic regulation of histone lactylation. Cell Rep. 42:1120332023. View Article : Google Scholar : PubMed/NCBI

34 

Wang X, Ying T, Yuan J, Wang Y, Su X, Chen S, Zhao Y, Zhao Y, Sheng J, Teng L, et al: BRAFV600E restructures cellular lactylation to promote anaplastic thyroid cancer proliferation. Endocr Relat Cancer. 30:e2203442023. View Article : Google Scholar : PubMed/NCBI

35 

Marcucci F and Rumio C: Tumor cell glycolysis-at the crossroad of epithelial-mesenchymal transition and autophagy. Cells. 11:10412022. View Article : Google Scholar : PubMed/NCBI

36 

Jia M, Yue X, Sun W, Zhou Q, Chang C, Gong W, Feng J, Li X, Zhan R, Mo K, et al: ULK1-mediated metabolic reprogramming regulates Vps34 lipid kinase activity by its lactylation. Sci Adv. 9:eadg49932023. View Article : Google Scholar : PubMed/NCBI

37 

Sun W, Jia M, Feng Y and Cheng X: Lactate is a bridge linking glycolysis and autophagy through lactylation. Autophagy. 19:3240–3241. 2023. View Article : Google Scholar : PubMed/NCBI

38 

Ashton TM, McKenna WG, Kunz-Schughart LA and Higgins GS: Oxidative phosphorylation as an emerging target in cancer therapy. Clin Cancer Res. 24:2482–2490. 2018. View Article : Google Scholar : PubMed/NCBI

39 

Sancho P, Barneda D and Heeschen C: Hallmarks of cancer stem cell metabolism. Br J Cancer. 114:1305–1312. 2016. View Article : Google Scholar : PubMed/NCBI

40 

Payen VL, Mina E, Van Hée VF, Porporato PE and Sonveaux P: Monocarboxylate transporters in cancer. Mol Metab. 33:48–66. 2020. View Article : Google Scholar : PubMed/NCBI

41 

Cheng Z, Huang H, Li M and Chen Y: Proteomic analysis identifies PFKP lactylation in SW480 colon cancer cells. iScience. 27:1086452023. View Article : Google Scholar

42 

Huang H, Wang S, Xia H, Zhao X, Chen K, Jin G, Zhou S, Lu Z, Chen T, Yu H, et al: Lactate enhances NMNAT1 lactylation to sustain nuclear NAD+ salvage pathway and promote survival of pancreatic adenocarcinoma cells under glucose-deprived conditions. Cancer Lett. 588:2168062024. View Article : Google Scholar

43 

Peng T, Sun F, Yang JC, Cai MH, Huai MX, Pan JX, Zhang FY and Xu LM: Novel lactylation-related signature to predict prognosis for pancreatic adenocarcinoma. World J Gastroenterol. 30:2575–2602. 2024. View Article : Google Scholar

44 

Jiang J, Huang D, Jiang Y, Hou J, Tian M, Li J, Sun L, Zhang Y, Zhang T, Li Z, et al: Lactate modulates cellular metabolism through histone lactylation-mediated gene expression in non-small cell lung cancer. Front Oncol. 11:6475592021. View Article : Google Scholar

45 

Daw CC, Ramachandran K, Enslow BT, Maity S, Bursic B, Novello MJ, Rubannelsonkumar CS, Mashal AH, Ravichandran J, Bakewell TM, et al: Lactate elicits ER-mitochondrial Mg2+ dynamics to integrate cellular metabolism. Cell. 183:474–489.e17. 2020. View Article : Google Scholar

46 

Zhang R, Li L and Yu J: Lactate-induced IGF1R protein lactylation promotes proliferation and metabolic reprogramming of lung cancer cells. Open Life Sci. 19:202208742024. View Article : Google Scholar

47 

Seo SH, Hwang SY, Hwang S, Han S, Park H, Lee YS, Rho SB and Kwon Y: Hypoxia-induced ELF3 promotes tumor angiogenesis through IGF1/IGF1R. EMBO Rep. 23:e529772022. View Article : Google Scholar : PubMed/NCBI

48 

Longhitano L, Vicario N, Tibullo D, Giallongo C, Broggi G, Caltabiano R, Barbagallo GMV, Altieri R, Baghini M, Di Rosa M, et al: Lactate induces the expressions of MCT1 and HCAR1 to promote tumor growth and progression in glioblastoma. Front Oncol. 12:8717982022. View Article : Google Scholar

49 

Longhitano L, Giallongo S, Orlando L, Broggi G, Longo A, Russo A, Caltabiano R, Giallongo C, Barbagallo I, Di Rosa M, et al: Lactate rewrites the metabolic reprogramming of uveal melanoma cells and induces quiescence phenotype. Int J Mol Sci. 24:242022. View Article : Google Scholar

50 

Yang L, Wang X, Liu J, Liu X, Li S, Zheng F, Dong Q, Xu S, Xiong J and Fu B: Prognostic and tumor microenvironmental feature of clear cell renal cell carcinoma revealed by m6A and lactylation modification-related genes. Front Immunol. 14:12250232023. View Article : Google Scholar

51 

Qu J, Li P and Sun Z: Histone lactylation regulates cancer progression by reshaping the tumor microenvironment. Front Immunol. 14:12843442023. View Article : Google Scholar

52 

Li F, Si W, Xia L, Yin D, Wei T, Tao M, Cui X, Yang J, Hong T and Wei R: Positive feedback regulation between glycolysis and histone lactylation drives oncogenesis in pancreatic ductal adenocarcinoma. Mol Cancer. 23:902024. View Article : Google Scholar : PubMed/NCBI

53 

Chen M, Cen K, Song Y, Zhang X, Liou YC, Liu P, Huang J, Ruan J, He J, Ye W, et al: NUSAP1-LDHA-glycolysis-lactate feedforward loop promotes Warburg effect and metastasis in pancreatic ductal adenocarcinoma. Cancer Lett. 567:2162852023. View Article : Google Scholar

54 

Qiao Z, Li Y, Li S, Liu S and Cheng Y: Hypoxia-induced SHMT2 protein lactylation facilitates glycolysis and stemness of esophageal cancer cells. Mol Cell Biochem. 479:3063–3076. 2024. View Article : Google Scholar : PubMed/NCBI

55 

Wei X, Chen Y, Jiang X, Peng M, Liu Y, Mo Y, Ren D, Hua Y, Yu B, Zhou Y, et al: Mechanisms of vasculogenic mimicry in hypoxic tumor microenvironments. Mol Cancer. 20:72021. View Article : Google Scholar : PubMed/NCBI

56 

Zhang M, Zhao Y, Liu X, Ruan X, Wang P, Liu L, Wang D, Dong W, Yang C and Xue Y: Pseudogene MAPK6P4-encoded functional peptide promotes glioblastoma vasculogenic mimicry development. Commun Biol. 6:10592023. View Article : Google Scholar

57 

Liu R, Zou Z, Chen L, Feng Y, Ye J, Deng Y, Zhu X, Zhang Y, Lin J, Cai S, et al: FKBP10 promotes clear cell renal cell carcinoma progression and regulates sensitivity to the HIF2α blockade by facilitating LDHA phosphorylation. Cell Death Dis. 15:642024. View Article : Google Scholar : PubMed/NCBI

58 

Luo Y, Yang Z, Yu Y and Zhang P: HIF1α lactylation enhances KIAA1199 transcription to promote angiogenesis and vasculogenic mimicry in prostate cancer. Int J Biol Macromol. 222:2225–2243. 2022. View Article : Google Scholar

59 

Meng Q, Sun H, Zhang Y, Yang X, Hao S, Liu B, Zhou H, Xu ZX and Wang Y: Lactylation stabilizes DCBLD1 activating the pentose phosphate pathway to promote cervical cancer progression. J Exp Clin Cancer Res. 43:362024. View Article : Google Scholar : PubMed/NCBI

60 

Meng Q, Zhang Y, Sun H, Yang X, Hao S, Liu B, Zhou H, Wang Y and Xu ZX: Human papillomavirus-16 E6 activates the pentose phosphate pathway to promote cervical cancer cell proliferation by inhibiting G6PD lactylation. Redox Biol. 71:1031082024. View Article : Google Scholar

61 

Wei S, Zhang J, Zhao R, Shi R, An L, Yu Z, Zhang Q, Zhang J, Yao Y, Li H and Wang H: Histone lactylation promotes malignant progression by facilitating USP39 expression to target PI3K/AKT/HIF-1α signal pathway in endometrial carcinoma. Cell Death Discov. 10:1212024. View Article : Google Scholar : PubMed/NCBI

62 

Zhao Y, Jiang J, Zhou P, Deng K, Liu Z, Yang M, Yang X, Li J, Li R and Xia J: H3K18 lactylation-mediated VCAM1 expression promotes gastric cancer progression and metastasis via AKT-mTOR-CXCL1 axis. Biochem Pharmacol. 222:1161202024. View Article : Google Scholar

63 

Li XM, Yang Y, Jiang FQ, Hu G, Wan S, Yan WY, He XS, Xiao F, Yang XM, Guo X, et al: Histone lactylation inhibits RARγ expression in macrophages to promote colorectal tumorigenesis through activation of TRAF6-IL-6-STAT3 signaling. Cell Rep. 43:1136882024. View Article : Google Scholar : PubMed/NCBI

64 

Liu M, Gu L, Zhang Y, Li Y, Zhang L, Xin Y, Wang Y and Xu ZX: LKB1 inhibits telomerase activity resulting in cellular senescence through histone lactylation in lung adenocarcinoma. Cancer Lett. 595:2170252024. View Article : Google Scholar

65 

Zheng P, Mao Z, Luo M, Zhou L, Wang L, Liu H, Liu W and Wei S: Comprehensive bioinformatics analysis of the solute carrier family and preliminary exploration of SLC25A29 in lung adenocarcinoma. Cancer Cell Int. 23:2222023. View Article : Google Scholar

66 

Li L, Li Z, Meng X, Wang X, Song D, Liu Y, Xu T, Qin J, Sun N, Tian K, et al: Histone lactylation-derived LINC01127 promotes the self-renewal of glioblastoma stem cells via the cis-regulating the MAP4K4 to activate JNK pathway. Cancer Lett. 579:2164672023. View Article : Google Scholar

67 

Yang J, Luo L, Zhao C, Li X, Wang Z, Zeng Z, Yang X, Zheng X, Jie H, Kang L, et al: A positive feedback loop between inactive VHL-triggered histone lactylation and PDGFRβ signaling drives clear cell renal cell carcinoma progression. Int J Biol Sci. 18:3470–3483. 2022. View Article : Google Scholar

68 

Jin J, Bai L, Wang D, Ding W, Cao Z, Yan P, Li Y, Xi L, Wang Y, Zheng X, et al: SIRT3-dependent delactylation of cyclin E2 prevents hepatocellular carcinoma growth. EMBO Rep. 24:e560522023. View Article : Google Scholar : PubMed/NCBI

69 

Liao J, Chen Z, Chang R, Yuan T, Li G, Zhu C, Wen J, Wei Y, Huang Z, Ding Z, et al: CENPA functions as a transcriptional regulator to promote hepatocellular carcinoma progression via cooperating with YY1. Int J Biol Sci. 19:5218–5232. 2023. View Article : Google Scholar

70 

Xie B, Zhang M, Li J, Cui J, Zhang P, Liu F, Wu Y, Deng W, Ma J, Li X, et al: KAT8-catalyzed lactylation promotes eEF1A2-mediated protein synthesis and colorectal carcinogenesis. Proc Natl Acad Sci USA. 121:e23141281212024. View Article : Google Scholar : PubMed/NCBI

71 

Xiong J, He J, Zhu J, Pan J, Liao W, Ye H, Wang H, Song Y, Du Y, Cui B, et al: Lactylation-driven METTL3-mediated RNA m6A modification promotes immunosuppression of tumor-infiltrating myeloid cells. Mol Cell. 82:1660–1677.e10. 2022. View Article : Google Scholar

72 

Yu J, Chai P, Xie M, Ge S, Ruan J, Fan X and Jia R: Histone lactylation drives oncogenesis by facilitating m6A reader protein YTHDF2 expression in ocular melanoma. Genome Biol. 22:852021. View Article : Google Scholar

73 

Gu X, Zhuang A, Yu J, Yang L, Ge S, Ruan J, Jia R, Fan X and Chai P: Histone lactylation-boosted ALKBH3 potentiates tumor progression and diminished promyelocytic leukemia protein nuclear condensates by m1A demethylation of SP100A. Nucleic Acids Res. 52:2273–2289. 2024. View Article : Google Scholar : PubMed/NCBI

74 

Chen B, Deng Y, Hong Y, Fan L, Zhai X, Hu H, Yin S, Chen Q, Xie X, Ren X, et al: Metabolic recoding of NSUN2-mediated m5c modification promotes the progression of colorectal cancer via the NSUN2/YBX1/m5C-ENO1 positive feedback loop. Adv Sci (Weinh). 11:e23098402024. View Article : Google Scholar : PubMed/NCBI

75 

Takata T, Nakamura A, Yasuda H, Miyake H, Sogame Y, Sawai Y, Hayakawa M, Mochizuki K, Nakao R, Ogata T, et al: Pathophysiological implications of protein lactylation in pancreatic epithelial tumors. Acta Histochem Cytochem. 57:57–66. 2024. View Article : Google Scholar : PubMed/NCBI

76 

Cai D, Yuan X, Cai DQ, Li A, Yang S, Yang W, Duan J, Zhuo W, Min J, Peng L and Wei J: Integrative analysis of lactylation-related genes and establishment of a novel prognostic signature for hepatocellular carcinoma. J Cancer Res Clin Oncol. 149:11517–11530. 2023. View Article : Google Scholar

77 

Yang H, Yang S, He J, Li W, Zhang A, Li N, Zhou G and Sun B: Glucose transporter 3 (GLUT3) promotes lactylation modifications by regulating lactate dehydrogenase A (LDHA) in gastric cancer. Cancer Cell Int. 23:3032023. View Article : Google Scholar

78 

Yang D, Yin J, Shan L, Yi X, Zhang W and Ding Y: Identification of lysine-lactylated substrates in gastric cancer cells. iScience. 25:1046302022. View Article : Google Scholar

79 

Hu X, Ouyang W, Chen H, Liu Z, Lai Z and Yao H: Claudin-9 (CLDN9) promotes gastric cancer progression by enhancing the glycolysis pathway and facilitating PD-L1 lactylation to suppress CD8+ T cell anti-tumor immunity. Cancer Pathog Ther. 3:253–266. 2024. View Article : Google Scholar : PubMed/NCBI

80 

Huang ZW, Zhang XN, Zhang L, Liu LL, Zhang JW, Sun YX, Xu JQ, Liu Q and Long ZJ: STAT5 promotes PD-L1 expression by facilitating histone lactylation to drive immunosuppression in acute myeloid leukemia. Signal Transduct Target Ther. 8:3912023. View Article : Google Scholar : PubMed/NCBI

81 

Gu J, Xu X, Li X, Yue L, Zhu X, Chen Q, Gao J, Takashi M, Zhao W, Zhao B, et al: Tumor-resident microbiota contributes to colorectal cancer liver metastasis by lactylation and immune modulation. Oncogene. 43:2389–2404. 2024. View Article : Google Scholar : PubMed/NCBI

82 

Wang J, Liu Z, Xu Y, Wang Y, Wang F, Zhang Q, Ni C, Zhen Y, Xu R, Liu Q, et al: Enterobacterial LPS-inducible LINC00152 is regulated by histone lactylation and promotes cancer cells invasion and migration. Front Cell Infect Microbiol. 12:9138152022. View Article : Google Scholar

83 

Hao B, Dong H, Xiong R, Song C, Xu C, Li N and Geng Q: Identification of SLC2A1 as a predictive biomarker for survival and response to immunotherapy in lung squamous cell carcinoma. Comput Biol Med. 171:1081832024. View Article : Google Scholar : PubMed/NCBI

84 

De Leo A, Ugolini A, Yu X, Scirocchi F, Scocozza D, Peixoto B, Pace A, D'Angelo L, Liu JKC, Etame AB, et al: Glucose-driven histone lactylation promotes the immunosuppressive activity of monocyte-derived macrophages in glioblastoma. Immunity. 57:1105–1123.e8. 2024. View Article : Google Scholar : PubMed/NCBI

85 

Lu X, Zhou Z, Qiu P and Xin T: Integrated single-cell and bulk RNA-sequencing data reveal molecular subtypes based on lactylation-related genes and prognosis and therapeutic response in glioma. Heliyon. 10:e307262024. View Article : Google Scholar : PubMed/NCBI

86 

Wu X, Mi T, Jin L, Ren C, Wang J, Zhang Z, Liu J, Wang Z, Guo P and He D: Dual roles of HK3 in regulating the network between tumor cells and tumor-associated macrophages in neuroblastoma. Cancer Immunol Immunother. 73:1222024. View Article : Google Scholar : PubMed/NCBI

87 

Wang ZH, Zhang P, Peng WB, Ye LL, Xiang X, Wei XS, Niu YR, Zhang SY, Xue QQ, Wang HL and Zhou Q: Altered phenotypic and metabolic characteristics of FOXP3+CD3+CD56+ natural killer T (NKT)-like cells in human malignant pleural effusion. Oncoimmunology. 12:21605582022. View Article : Google Scholar : PubMed/NCBI

88 

Hong H, Chen X, Wang H, Gu X, Yuan Y and Zhang Z: Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma. Proteomics. 23:e22004322023. View Article : Google Scholar : PubMed/NCBI

89 

Cheng Z, Huang H, Li M, Liang X, Tan Y and Chen Y: Lactylation-related gene signature effectively predicts prognosis and treatment responsiveness in hepatocellular carcinoma. Pharmaceuticals (Basel). 16:6442023. View Article : Google Scholar : PubMed/NCBI

90 

Wu Q, Li X, Long M, Xie X and Liu Q: Integrated analysis of histone lysine lactylation (Kla)-specific genes suggests that NR6A1, OSBP2 and UNC119B are novel therapeutic targets for hepatocellular carcinoma. Sci Rep. 13:186422023. View Article : Google Scholar : PubMed/NCBI

91 

Lai JP, Sandhu DS, Moser CD, Cazanave SC, Oseini AM, Shire AM, Shridhar V, Sanderson SO and Roberts LR: Additive effect of apicidin and doxorubicin in sulfatase 1 expressing hepatocellular carcinoma in vitro and in vivo. J Hepatol. 50:1112–1121. 2009. View Article : Google Scholar

92 

Wang Y, Pei P, Yang K, Guo L and Li Y: Copper in colorectal cancer: From copper-related mechanisms to clinical cancer therapies. Clin Transl Med. 14:e17242024. View Article : Google Scholar : PubMed/NCBI

93 

Sun L, Zhang Y, Yang B, Sun S, Zhang P, Luo Z, Feng T, Cui Z, Zhu T, Li Y, et al: Lactylation of METTL16 promotes cuproptosis via m6A-modification on FDX1 mRNA in gastric cancer. Nat Commun. 14:65232023. View Article : Google Scholar : PubMed/NCBI

94 

Li W, Zhou C, Yu L, Hou Z, Liu H, Kong L, Xu Y, He J, Lan J, Ou Q, et al: Tumor-derived lactate promotes resistance to bevacizumab treatment by facilitating autophagy enhancer protein RUBCNL expression through histone H3 lysine 18 lactylation (H3K18la) in colorectal cancer. Autophagy. 20:114–130. 2024. View Article : Google Scholar : PubMed/NCBI

95 

Sun X, He L, Liu H, Thorne RF, Zeng T, Liu L, Zhang B, He M, Huang Y, Li M, et al: The diapause-like colorectal cancer cells induced by SMC4 attenuation are characterized by low proliferation and chemotherapy insensitivity. Cell Metab. 35:1563–1579.e8. 2023. View Article : Google Scholar : PubMed/NCBI

96 

Chu YD, Cheng LC, Lim SN, Lai MW, Yeh CT and Lin WR: Aldolase B-driven lactagenesis and CEACAM6 activation promote cell renewal and chemoresistance in colorectal cancer through the Warburg effect. Cell Death Dis. 14:6602023. View Article : Google Scholar : PubMed/NCBI

97 

Brown TP and Ganapathy V: Lactate/GPR81 signaling and proton motive force in cancer: Role in angiogenesis, immune escape, nutrition, and Warburg phenomenon. Pharmacol Ther. 206:1074512020. View Article : Google Scholar : PubMed/NCBI

98 

Xia L, Oyang L, Lin J, Tan S, Han Y, Wu N, Yi P, Tang L, Pan Q, Rao S, et al: The cancer metabolic reprogramming and immune response. Mol Cancer. 20:282021. View Article : Google Scholar : PubMed/NCBI

99 

Yan F, Teng Y, Li X, Zhong Y, Li C, Yan F and He X: Hypoxia promotes non-small cell lung cancer cell stemness, migration, and invasion via promoting glycolysis by lactylation of SOX9. Cancer Biol Ther. 25:23041612024. View Article : Google Scholar : PubMed/NCBI

100 

Duan W, Liu W, Xia S, Zhou Y, Tang M, Xu M, Lin M, Li X and Wang Q: Warburg effect enhanced by AKR1B10 promotes acquired resistance to pemetrexed in lung cancer-derived brain metastasis. J Transl Med. 21:5472023. View Article : Google Scholar : PubMed/NCBI

101 

Zheng H, Peng X, Yang S, Li X, Huang M, Wei S, Zhang S, He G, Liu J, Fan Q, et al: Targeting tumor-associated macrophages in hepatocellular carcinoma: Biology, strategy, and immunotherapy. Cell Death Discov. 9:652023. View Article : Google Scholar : PubMed/NCBI

102 

Li F, Zhang H, Huang Y, Li D, Zheng Z, Xie K, Cao C, Wang Q, Zhao X, Huang Z, et al: Single-cell transcriptome analysis reveals the association between histone lactylation and cisplatin resistance in bladder cancer. Drug Resist Updat. 73:1010592024. View Article : Google Scholar

103 

Li K, Chen MK, Li LY, Lu MH, Shao ChK, Su ZL, He D, Pang J and Gao X: The predictive value of semaphorins 3 expression in biopsies for biochemical recurrence of patients with low- and intermediate-risk prostate cancer. Neoplasma. 60:683–689. 2013. View Article : Google Scholar

104 

Pan J, Zhang J, Lin J, Cai Y and Zhao Z: Constructing lactylation-related genes prognostic model to effectively predict the disease-free survival and treatment responsiveness in prostate cancer based on machine learning. Front Genet. 15:13431402024. View Article : Google Scholar

105 

Chaudagar K, Hieromnimon HM, Khurana R, Labadie B, Hirz T, Mei S, Hasan R, Shafran J, Kelley A, Apostolov E, et al: Reversal of lactate and PD-1-mediated macrophage immunosuppression controls growth of PTEN/p53-deficient prostate cancer. Clin Cancer Res. 29:1952–1968. 2023. View Article : Google Scholar : PubMed/NCBI

106 

Chaudagar K, Hieromnimon HM, Kelley A, Labadie B, Shafran J, Rameshbabu S, Drovetsky C, Bynoe K, Solanki A, Markiewicz E, et al: Suppression of tumor cell lactate-generating signaling pathways eradicates murine PTEN/p53-deficient aggressive-variant prostate cancer via macrophage phagocytosis. Clin Cancer Res. 29:4930–4940. 2023. View Article : Google Scholar : PubMed/NCBI

107 

Zhang XW, Li L, Liao M, Liu D, Rehman A, Liu Y, Liu ZP, Tu PF and Zeng KW: Thermal proteome profiling strategy identifies CNPY3 as a cellular target of gambogic acid for inducing prostate cancer pyroptosis. J Med Chem. 67:10005–10011. 2024. View Article : Google Scholar : PubMed/NCBI

108 

Jiao Y, Ji F, Hou L, Lv Y and Zhang J: Lactylation-related gene signature for prognostic prediction and immune infiltration analysis in breast cancer. Heliyon. 10:e247772024. View Article : Google Scholar : PubMed/NCBI

109 

Deng J and Liao X: Lysine lactylation (Kla) might be a novel therapeutic target for breast cancer. BMC Med Genomics. 16:2832023. View Article : Google Scholar : PubMed/NCBI

110 

Yu L, Jing C, Zhuang S, Ji L and Jiang L: A novel lactylation-related gene signature for effectively distinguishing and predicting the prognosis of ovarian cancer. Transl Cancer Res. 13:2497–2508. 2024. View Article : Google Scholar : PubMed/NCBI

111 

Zhu Y and Song B, Yang Z, Peng Y, Cui Z, Chen L and Song B: Integrative lactylation and tumor microenvironment signature as prognostic and therapeutic biomarkers in skin cutaneous melanoma. J Cancer Res Clin Oncol. 149:17897–17919. 2023. View Article : Google Scholar

112 

Feng H, Chen W and Zhang C: Identification of lactylation gene CALML5 and its correlated lncRNAs in cutaneous melanoma by machine learning. Medicine (Baltimore). 102:e359992023. View Article : Google Scholar : PubMed/NCBI

113 

Pan L, Feng F, Wu J, Fan S, Han J, Wang S, Yang L, Liu W, Wang C and Xu K: Demethylzeylasteral targets lactate by inhibiting histone lactylation to suppress the tumorigenicity of liver cancer stem cells. Pharmacol Res. 181:1062702022. View Article : Google Scholar : PubMed/NCBI

114 

Gong H, Xu HM, Ma YH and Zhang DK: Demethylzeylasteral targets lactate to suppress the tumorigenicity of liver cancer stem cells: It is attributed to histone lactylation? Pharmacol Res. 194:1068692023. View Article : Google Scholar : PubMed/NCBI

115 

Wang C, Feng F, Pan L and Xu K: Reply to the letter titled: Demethylzeylasteral targets lactate to suppress the tumorigenicity of liver cancer stem cells: Is it attributed to histone lactylation? Pharmacol Res. 194:1068682023. View Article : Google Scholar : PubMed/NCBI

116 

Xu H, Li L, Wang S, Wang Z, Qu L, Wang C and Xu K: Royal jelly acid suppresses hepatocellular carcinoma tumorigenicity by inhibiting H3 histone lactylation at H3K9la and H3K14la sites. Phytomedicine. 118:1549402023. View Article : Google Scholar : PubMed/NCBI

117 

Guo Z, Tang Y, Wang S, Huang Y, Chi Q, Xu K and Xue L: Natural product fargesin interferes with H3 histone lactylation via targeting PKM2 to inhibit non-small cell lung cancer tumorigenesis. Biofactors. 50:592–607. 2024. View Article : Google Scholar : PubMed/NCBI

118 

Gu J, Zhou J, Chen Q, Xu X, Gao J, Li X, Shao Q, Zhou B, Zhou H, Wei S, et al: Tumor metabolite lactate promotes tumorigenesis by modulating MOESIN lactylation and enhancing TGF-β signaling in regulatory T cells. Cell Rep. 39:1109862022. View Article : Google Scholar : PubMed/NCBI

119 

Yue Q, Wang Z, Shen Y, Lan Y, Zhong X, Luo X, Yang T, Zhang M, Zuo B, Zeng T, et al: Histone H3K9 lactylation confers temozolomide resistance in glioblastoma via LUC7L2-Mediated MLH1 intron retention. Adv Sci (Weinh). 11:e23092902024. View Article : Google Scholar : PubMed/NCBI

120 

Sun T, Liu B, Li Y, Wu J, Cao Y, Yang S, Tan H, Cai L, Zhang S, Qi X, et al: Oxamate enhances the efficacy of CAR-T therapy against glioblastoma via suppressing ectonucleotidases and CCR8 lactylation. J Exp Clin Cancer Res. 42:2532023. View Article : Google Scholar : PubMed/NCBI

121 

Hu X, Wang J, Chu M, Liu Y, Wang ZW and Zhu X: Emerging role of ubiquitination in the regulation of PD-1/PD-L1 in cancer immunotherapy. Mol Ther. 29:908–919. 2021. View Article : Google Scholar : PubMed/NCBI

122 

Yu Y, Huang X, Liang C and Zhang P: Evodiamine impairs HIF1A histone lactylation to inhibit Sema3A-mediated angiogenesis and PD-L1 by inducing ferroptosis in prostate cancer. Eur J Pharmacol. 957:1760072023. View Article : Google Scholar

123 

Cui Z, Li Y, Lin Y, Zheng C, Luo L, Hu D, Chen Y, Xiao Z and Sun Y: Lactylproteome analysis indicates histone H4K12 lactylation as a novel biomarker in triple-negative breast cancer. Front Endocrinol (Lausanne). 15:13286792024. View Article : Google Scholar : PubMed/NCBI

124 

Galle E, Wong CW, Ghosh A, Desgeorges T, Melrose K, Hinte LC, Castellano-Castillo D, Engl M, de Sousa JA, Ruiz-Ojeda FJ, et al: H3K18 lactylation marks tissue-specific active enhancers. Genome Biol. 23:2072022. View Article : Google Scholar

125 

Fan W, Zeng S, Wang X, Wang G, Liao D, Li R, He S, Li W, Huang J, Li X, et al: A feedback loop driven by H3K9 lactylation and HDAC2 in endothelial cells regulates VEGF-induced angiogenesis. Genome Biol. 25:1652024. View Article : Google Scholar

126 

Dai W, Wu G, Liu K, Chen Q, Tao J, Liu H and Shen M: Lactate promotes myogenesis via activating H3K9 lactylation-dependent up-regulation of Neu2 expression. J Cachexia Sarcopenia Muscle. 14:2851–2865. 2023. View Article : Google Scholar : PubMed/NCBI

127 

Li X, Chen M, Chen X, He X, Li X, Wei H, Tan Y, Min J, Azam T, Xue M, et al: TRAP1 drives smooth muscle cell senescence and promotes atherosclerosis via HDAC3-primed histone H4 lysine 12 lactylation. Eur Heart J. 45:4219–4235. 2024. View Article : Google Scholar : PubMed/NCBI

128 

Chen H, Li Y, Li H, Chen X, Fu H, Mao D, Chen W, Lan L, Wang C, Hu K, et al: NBS1 lactylation is required for efficient DNA repair and chemotherapy resistance. Nature. 631:663–669. 2024. View Article : Google Scholar : PubMed/NCBI

129 

Chen Y, Wu J, Zhai L, Zhang T, Yin H, Gao H, Zhao F, Wang Z, Yang X, Jin M, et al: Metabolic regulation of homologous recombination repair by MRE11 lactylation. Cell. 187:294–311.e21. 2024. View Article : Google Scholar

130 

Zhou C, Li W, Liang Z, Wu X, Cheng S, Peng J, Zeng K, Li W, Lan P, Yang X, et al: Mutant KRAS-activated circATXN7 fosters tumor immunoescape by sensitizing tumor-specific T cells to activation-induced cell death. Nat Commun. 15:4992024. View Article : Google Scholar : PubMed/NCBI

131 

Deng D, Luo Y, Hong Y, Ren X, Zu X and Feng J: Lactylation: A new direction for tumor-targeted therapy. Biochim Biophys Acta Rev Cancer. 1880:1893992025. View Article : Google Scholar : PubMed/NCBI

132 

Hou X, Hong Z, Zen H, Zhang C, Zhang P, Ma D and Han Z: Lactylation in cancer biology: Unlocking new avenues for research and therapy. Cancer Commun (Lond). Aug 19–2025.(Epub ahead of print). View Article : Google Scholar

133 

Jin J, Yan P, Wang D, Bai L, Liang H, Zhu X, Zhu H, Ding C, Wei H and Wang Y: Targeting lactylation reinforces NK cell cytotoxicity within the tumor microenvironment. Nat Immunol. 26:1099–1112. 2025. View Article : Google Scholar

134 

Li X, Zhang C, Mei Y, Zhong W, Fan W, Liu L, Feng Z, Bai X, Liu C, Xiao M, et al: Irinotecan alleviates chemoresistance to anthracyclines through the inhibition of AARS1-mediated BLM lactylation and homologous recombination repair. Signal Transduct Target Ther. 10:2142025. View Article : Google Scholar : PubMed/NCBI

135 

Peng X and Du J: Histone and non-histone lactylation: Molecular mechanisms, biological functions, diseases, and therapeutic targets. Mol Biomed. 6:382025. View Article : Google Scholar : PubMed/NCBI

136 

Chen X, Yuan Y, Zhou F, Li L, Pu J, Zeng Y and Jiang X: Lactylation: From homeostasis to pathological implications and therapeutic strategies. MedComm (2020). 6:e702262025. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Wang X, Chen J, Wang B, Li Y, Zhou X, Song Y, Miao C and Huang Y: Impact of lactylation on the pathogenesis of cancer and its clinical application potential (Review). Mol Med Rep 32: 336, 2025.
APA
Wang, X., Chen, J., Wang, B., Li, Y., Zhou, X., Song, Y. ... Huang, Y. (2025). Impact of lactylation on the pathogenesis of cancer and its clinical application potential (Review). Molecular Medicine Reports, 32, 336. https://doi.org/10.3892/mmr.2025.13702
MLA
Wang, X., Chen, J., Wang, B., Li, Y., Zhou, X., Song, Y., Miao, C., Huang, Y."Impact of lactylation on the pathogenesis of cancer and its clinical application potential (Review)". Molecular Medicine Reports 32.6 (2025): 336.
Chicago
Wang, X., Chen, J., Wang, B., Li, Y., Zhou, X., Song, Y., Miao, C., Huang, Y."Impact of lactylation on the pathogenesis of cancer and its clinical application potential (Review)". Molecular Medicine Reports 32, no. 6 (2025): 336. https://doi.org/10.3892/mmr.2025.13702
Copy and paste a formatted citation
x
Spandidos Publications style
Wang X, Chen J, Wang B, Li Y, Zhou X, Song Y, Miao C and Huang Y: Impact of lactylation on the pathogenesis of cancer and its clinical application potential (Review). Mol Med Rep 32: 336, 2025.
APA
Wang, X., Chen, J., Wang, B., Li, Y., Zhou, X., Song, Y. ... Huang, Y. (2025). Impact of lactylation on the pathogenesis of cancer and its clinical application potential (Review). Molecular Medicine Reports, 32, 336. https://doi.org/10.3892/mmr.2025.13702
MLA
Wang, X., Chen, J., Wang, B., Li, Y., Zhou, X., Song, Y., Miao, C., Huang, Y."Impact of lactylation on the pathogenesis of cancer and its clinical application potential (Review)". Molecular Medicine Reports 32.6 (2025): 336.
Chicago
Wang, X., Chen, J., Wang, B., Li, Y., Zhou, X., Song, Y., Miao, C., Huang, Y."Impact of lactylation on the pathogenesis of cancer and its clinical application potential (Review)". Molecular Medicine Reports 32, no. 6 (2025): 336. https://doi.org/10.3892/mmr.2025.13702
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