蛋白乳酸化修饰及其在肝胆胰肿瘤中的研究进展

doi:10.3877/cma.j.issn.2095-3232.2026.04.021

蛋白乳酸化修饰作为一种新发现的翻译后修饰形式，近年来在肿瘤生物学领域引起了广泛的关注。肝胆胰肿瘤是消化系统中发病率高且预后较差的恶性肿瘤，其复杂的发生和发展机制亟需深入探讨。通过调节肿瘤细胞的代谢重编程、促进细胞增殖及介导免疫逃逸等多种途径，蛋白乳酸化修饰逐渐成为理解肝胆胰肿瘤生物学特性的重要切入点。本文系统综述了蛋白乳酸化的分子机制及其检测方法，重点评述其在肝胆胰肿瘤中的功能作用和临床应用潜力，结合最新研究进展，探讨该领域面临的挑战与未来发展趋势，旨在为基础研究和临床治疗策略的优化提供理论依据和新思路。

关键词: 蛋白乳酸化, 肝胆胰肿瘤, 翻译后修饰, 肿瘤代谢, 免疫调控

As a novel type of post-translational modification, protein lactylation has captivated extensive attention in the field of tumor biology in recent years. Hepatobiliary and pancreatic tumors are a type of malignant tumors in the digestive system with high incidence and poor prognosis. The complicated mechanism of incidence and development remains to be urgently unraveled. By regulating the metabolic reprogramming of tumor cells, promoting cell proliferation and mediating immune escape, protein lactylation has gradually become an important breakthrough point to understand the biological characteristics of hepatobiliary and pancreatic tumors. In this article, the molecular mechanism and detection methods of protein lactylation were systematically reviewed. The functional role and the potential of clinical application in hepatobiliary and pancreatic tumors were highlighted. Combined with the latest research progress, the challenges and future development trends in this field were illustrated, aiming to provide theoretical basis and novel ideas for optimizing basic research and clinical treatment strategies.

Key words: Protein lactylation, Hepatobiliary pancreatic tumors, Post-translational modification, Tumor metabolism, Immune regulation

[1]	Zhang D, Tang Z, Huang H, et al. Metabolic regulation of gene expression by histone lactylation[J]. Nature, 2019, 574(7779): 575-580. DOI: 10.1038/s41586-019-1678-1.
[2]	陈雪雷, 葛菲, 万梦琪, 等. 乳酸经Akt信号途径促进胃癌细胞中高迁移率族蛋白盒1的磷酸化及释放[J]. 中华肿瘤杂志, 2023, 45(11): 919-925. DOI: 10.3760/cma.j.cn112152-20220901-00590.
[3]	吴茹霞, 解震, 杜洋洋, 等. 乳酸化修饰在肝细胞癌发展中作用的研究进展[J]. 生命科学, 2026, 38(1): 70-81. DOI: 10.3724/cbls.2026012.
[4]	伍燕钦, 李春震, 于益芝. 组蛋白乳酸化修饰在肿瘤中的研究进展[J]. 中国肿瘤生物治疗杂志, 2025, 32(10): 1078-1083. DOI: 10.3872/j.issn.1007-385x.2025.10.011.
[5]	张自越, 周聪, 张子轩, 等. 乳酸化修饰在肝癌发生发展中的作用研究进展[J]. 中国细胞生物学学报, 2025, 47(6): 1396-1404. DOI: 10.11844/cjcb.2025.06.0017.
[6]	郭馨蔚, 余和芬. 蛋白质乳酸化修饰在肿瘤代谢和肿瘤免疫中的作用[J]. 生命的化学, 2025, 45(2): 324-331. DOI: 10.13488/j.smhx.20250517.
[7]	Li D, Wang K, Lou G, et al. Navigating the role of protein lactylation in prostate cancer and its implications for immunotherapy[J]. J Cancer, 2025, 16(8): 2706-2719. DOI: 10.7150/jca.114137.
[8]	Jia J, Liu N, Zhu X, et al. Insights into recent findings and therapeutic potential of nonhistone lactylation in cancer[J]. Front Mol Biosci, 2025, 12: 1661697. DOI: 10.3389/fmolb.2025.1661697.
[9]	Deng D, Luo Y, Hong Y, et al. Lactylation: a new direction for tumor-targeted therapy[J]. Biochim Biophys Acta BBA Rev Cancer, 2025, 1880(5): 189399. DOI: 10.1016/j.bbcan.2025.189399.
[10]	Zhao C, Wan Q, Zhao R. The role of pyruvate kinase M2 posttranslational modification in the occurrence and development of hepatocellular carcinoma[J]. Cell Biochem Funct, 2024, 42(7): e4125. DOI: 10.1002/cbf.4125.
[11]	Wang ZH, Peng WB, Zhang P, et al. Lactate in the tumour microenvironment: from immune modulation to therapy[J]. EBioMedicine, 2021, 73: 103627. DOI: 10.1016/j.ebiom.2021.103627.
[12]	李永昭, 米晨, 王栋栋, 等. 乳酸化在消化系统肿瘤中的研究进展[J]. 中国细胞生物学学报, 2025, 47(6): 1464-1476. DOI: 10.11844/cjcb.2025.06.0023.
[13]	Wang X, Chen J, Wang B, et al. Impact of lactylation on the pathogenesis of cancer and its clinical application potential (Review)[J]. Mol Med Rep, 2025, 32(6): 1-17. DOI: 10.3892/mmr.2025.13702.
[14]	Qiu Y, Wen J, Jia N, et al. Decoding the lactylation landscape: implications for tumor microenvironment remodeling and marine algal saccharide-based therapeutic interventions[J]. Phytomedicine, 2025, 147: 157169. DOI: 10.1016/j.phymed.2025.157169.
[15]	Wang J, Wang Z, Wang Q, et al. Ubiquitous protein lactylation in health and diseases[J]. Cell Mol Biol Lett, 2024, 29(1): 23. DOI: 10.1186/s11658-024-00541-5.
[16]	Gao L, Guo J, Jia R. AARS1 and AARS2: from protein synthesis to lactylation-driven oncogenesis[J]. Biomolecules, 2025, 15(9): 1323. DOI: 10.3390/biom15091323.
[17]	Shi CM, Wang QC, Li XL, et al. Global profiling of protein lactylation in human hippocampi[J]. Proteomics Clin Appl, 2025, 19(2): e202400061. DOI: 10.1002/prca.202400061.
[18]	Wu D, Tang Y, Li X, et al. Characterization of protein lactylation in healthy and ischemic mouse hearts[J]. Front Cardiovasc Med, 2025, 12: 1644886. DOI: 10.3389/fcvm.2025.1644886.
[19]	Li C, Fu C, Zhou W, et al. Lactylation modification of HIF-1α enhances its stability by blocking VHL recognition[J]. Cell Commun Signal, 2025, 23(1): 364. DOI: 10.1186/s12964-025-02366-x.
[20]	Shu M, Lu D, Zhu Z, et al. Insight into the roles of lactylation in macrophages: functions and clinical implications[J]. Clin Sci, 2025, 139(2): 151-169. DOI: 10.1042/cs20242737.
[21]	Wang M, He T, Meng D, et al. BZW2 modulates lung adenocarcinoma progression through glycolysis-mediated IDH3G lactylation modification[J]. J Proteome Res, 2023, 22(12): 3854-3865. DOI: 10.1021/acs.jproteome.3c00518.
[22]	Liu S, Cai J, Qian X, et al. TPX2 lactylation is required for the cell cycle regulation and hepatocellular carcinoma progression[J]. Life Sci Alliance, 2025, 8(6): e202402978. DOI: 10.26508/lsa.202402978.
[23]	Liao J, Chen Z, Chang R, et al. CENPA functions as a transcriptional regulator to promote hepatocellular carcinoma progression via cooperating with YY1[J]. Int J Biol Sci, 2023, 19(16): 5218-5232. DOI: 10.7150/ijbs.85656.
[24]	Du W, Tan S, Peng Y, et al. Histone lactylation-driven YTHDC1 promotes hepatocellular carcinoma progression via lipid metabolism remodeling[J]. Cancer Lett, 2024, 611: 217426. DOI: 10.1016/j.canlet.2024.217426.
[25]	Yang Z, Yan C, Ma J, et al. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma[J]. Nat Metab, 2023, 5(1): 61-79. DOI: 10.1038/s42255-022-00710-w.
[26]	Jiang C, He X, Chen X, et al. Lactate accumulation drives hepatocellular carcinoma metastasis through facilitating tumor-derived exosome biogenesis by Rab7A lactylation[J]. Cancer Lett, 2025, 627: 217636. DOI: 10.1016/j.canlet.2025.217636.
[27]	Huang J, Xie H, Li J, et al. Histone lactylation drives liver cancer metastasis by facilitating NSF1-mediated ferroptosis resistance after microwave ablation[J]. Redox Biol, 2025, 81: 103553. DOI: 10.1016/j.redox.2025.103553.
[28]	Yang L, Niu K, Wang J, et al. Nucleolin lactylation contributes to intrahepatic cholangiocarcinoma pathogenesis via RNA splicing regulation of MADD[J]. J Hepatol, 2024, 81(4): 651-666. DOI: 10.1016/j.jhep.2024.04.010.
[29]	Xie W, Hu J, Xu H. Integrated transcriptomic analysis identifies lactylation-linked gemcitabine resistance and therapeutic targets in intrahepatic cholangiocarcinoma[J]. Front Cell Dev Biol, 2025, 13: 1611434. DOI: 10.3389/fcell.2025.1611434.
[30]	Wang T, Ye Z, Li Z, et al. Lactate-induced protein lactylation: a bridge between epigenetics and metabolic reprogramming in cancer[J]. Cell Prolif, 2023, 56(10): e13478. DOI: 10.1111/cpr.13478.
[31]	Peng T, Sun F, Yang JC, et al. Novel lactylation-related signature to predict prognosis for pancreatic adenocarcinoma[J]. World J Gastroenterol, 2024, 30(19): 2575-2602. DOI: 10.3748/wjg.v30.i19.2575.
[32]	黄天浩. 乳酸化修饰的NSUN2促进胰腺癌的周围神经浸润[D]. 广州: 南方医科大学, 2025. DOI: 10.27003/d.cnki.gojyu.2025.001416.
[33]	冯静怡. H2AX乳酸化促进胰腺癌放疗后DNA损伤修复的机制研究[D]. 镇江: 江苏大学, 2024. DOI: 10.27170/d.cnki.gjsuu.2024.002052.
[34]	Hou J, Guo M, Li Y, et al. Lactylated histone H3K18 as a potential biomarker for the diagnosis and prediction of the severity of pancreatic cancer[J]. Clinics, 2024, 80: 100544. DOI: 10.1016/j.clinsp.2024.100544.
[35]	Saeed MM, Ma X, Fu X, et al. RACGAP1 and MKI67 are potential prognostic biomarker in hepatocellular carcinoma caused by HBV/HCV via lactylation[J]. Front Oncol, 2025, 15: 1537084. DOI: 10.3389/fonc.2025.1537084.
[36]	Han H, Wang S, Ma L, et al. ASH2L-K312-lac stimulates angiogenesis in tumors to expedite the malignant progression of hepatocellular carcinoma[J]. Adv Sci, 2025, 12(40): e09477. DOI: 10.1002/advs.202509477.
[37]	Yu D, Zhong Q, Wang Y, et al. Lactylation: the metabolic accomplice shaping cancer's response to radiotherapy and immunotherapy[J]. Ageing Res Rev, 2025, 104: 102670. DOI: 10.1016/j.arr.2025.102670.
[38]	He Y, Song T, Ning J, et al. Lactylation in cancer: mechanisms in tumour biology and therapeutic potentials[J]. Clin Transl Med, 2024, 14(11): e70070. DOI: 10.1002/ctm2.70070.
[39]	Wang D, Rong H, Ma K, et al. Lactylation in tumor: mechanisms and therapeutic potentials[J]. Front Immunol, 2025, 16: 1609596. DOI: 10.3389/fimmu.2025.1609596.
[40]	Wang Y, Chen J, Wang Y, et al. Pharmacologically targeting protein lactylation to overcome cancer drug resistance[J]. Eur J Med Chem, 2025, 296: 117905. DOI: 10.1016/j.ejmech.2025.117905.
[41]	Xu K, Shou Y, Liu R, et al. Lactylation in cancer: advances and opportunities for treatment resistance[J]. Clin Transl Med, 2025, 15(10): e70478. DOI: 10.1002/ctm2.70478.
[42]	Ghadyani F, Zandi P, Ghafouri-Fard S. Histone lactylation: a new target for overcoming immune evasion and therapy resistance[J]. Med Oncol, 2025, 42(9): 399. DOI: 10.1007/s12032-025-02940-w.

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Research progress in protein lactylation in hepatobiliary and pancreatic tumors

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Research progress in protein lactylation in hepatobiliary and pancreatic tumors