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References from Non-histone protein lactylation in cancer metastasis: From metabolic reprogramming to therapeutic targeting. Local targets link to admitted publications; unresolved targets remain external evidence.
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Lactate in the tumor microenvironment: an essential molecule in cancer progression and treatment
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Lactate: a metabolic driver in the tumour landscape
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Tumor microenvironment lactate: is it a cancer progression marker, immunosuppressant, and therapeutic target?
10.3390/molecules30081763 · 2025 · External reference
Metabolic regulation of gene expression by histone lactylation
10.1038/s41586-019-1678-1 · 2019 · External reference
The cancer metabolic reprogramming and immune response
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Systematic and comprehensive insights into HIF-1 stabilization under normoxic conditions: implications for cellular adaptation and therapeutic strategies in cancer
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ULK1-mediated metabolic reprogramming regulates Vps34 lipid kinase activity by its lactylation
10.1126/sciadv.adg4993 · 2023 · External reference
10.1016/j.cell.2023.11.022
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Tumor metabolite lactate promotes tumorigenesis by modulating MOESIN lactylation and enhancing TGF-β signaling in regulatory T cells
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Reversible inactivation of HIF-1 prolyl hydroxylases allows cell metabolism to control basal HIF-1
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Lactate and lactylation in cancer
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Dexmedetomidine inhibits the migration, invasion, and glycolysis of glioblastoma cells by lactylation of c-myc
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HSPA12A promotes c-Myc lactylation-mediated proliferation of tubular epithelial cells to facilitate renal functional recovery from kidney ischemia/reperfusion injury
10.1007/s00018-024-05427-5 · 2024 · External reference
ICAT drives lactylation of tumor-associated macrophages via the c-Myc-ENO1 axis to promote cervical cancer progression
2025 · External reference
Lactate induced c-Myc lactylation drives prostate cancer progression by influencing gene transcription
10.1158/1538-7445.am2025-1539 · 2025 · External reference
Lactylation of PKM2 suppresses inflammatory metabolic adaptation in pro-inflammatory macrophages
10.7150/ijbs.75434 · 2022 · External reference
Tumour invasion and dissemination
10.1042/bst20220452 · 2022 · External reference
Epithelial-to-mesenchymal transition (EMT) and cancer metastasis: the status quo of methods and experimental models 2025
10.1186/s12943-025-02338-2 · 2025 · External reference
Epithelial–mesenchymal transition and its transcription factors
10.1042/bsr20211754 · 2022 · External reference
Lactate promotes the epithelial-mesenchymal transition of liver cancer cells via TWIST1 lactylation
10.1016/j.yexcr.2025.114474 · 2025 · External reference
RHOF promotes Snail1 lactylation by enhancing PKM2-mediated glycolysis to induce pancreatic cancer cell endothelial–mesenchymal transition
10.1186/s40170-024-00362-2 · 2024 · External reference
Lactate promotes endothelial-to-mesenchymal transition via Snail1 lactylation after myocardial infarction
10.1126/sciadv.adc9465 · 2023 · External reference
The mechanism of PFK-1 in the occurrence and development of bladder cancer by regulating ZEB1 lactylation
10.1186/s12894-024-01444-5 · 2024 · External reference
The function and mechanism of lactate and lactylation in tumor metabolism and microenvironment
10.1016/j.gendis.2022.10.006 · 2023 · External reference
Lactate and lactylation in cancer: drivers of immune suppression and microenvironmental reprogramming
10.1186/s40164-025-00719-3 · 2025 · External reference
Lactylation: a novel driver of drug resistance in the tumor microenvironment
2025 · External reference
Lactate-mediated metabolic reprogramming of tumor-associated macrophages: Implications for tumor progression and therapeutic potential
10.3389/fimmu.2025.1573039 · 2025 · External reference
Functional polarization of tumor-associated macrophages dictated by metabolic reprogramming
10.1186/s13046-023-02832-9 · 2023 · External reference
The roles of tumor-associated macrophages in tumor angiogenesis and metastasis
10.1016/j.cellimm.2020.104119 · 2020 · External reference
The impact of the tumor microenvironment on macrophage polarization in cancer metastatic progression
10.3390/ijms22126560 · 2021 · External reference
The role of tumor associated macrophages (TAMs) in cancer progression, chemoresistance, angiogenesis and metastasis-current status
10.2174/0929867328666210720143721 · 2021 · External reference
Exploring the mechanisms of mutual influence between lactylation and macrophage polarization in the context of disease
10.1002/ctm2.70499 · 2025 · External reference
Insight into the roles of lactylation in macrophages: functions and clinical implications
10.1042/cs20242737 · 2025 · External reference
Lactate: a multifunctional signaling molecule
10.12701/yujm.2020.00892 · 2021 · External reference
Lactylation: the novel histone modification influence on gene expression, protein function, and disease
10.1186/s13148-024-01682-2 · 2024 · External reference
10.1016/j.cmet.2024.10.015
10.1016/j.cmet.2024.10.015 · External reference
10.1016/j.cmet.2024.11.005
10.1016/j.cmet.2024.11.005 · External reference
SIRT2 functions as a histone delactylase and inhibits the proliferation and migration of neuroblastoma cells
10.1038/s41421-022-00398-y · 2022 · External reference
Class I histone deacetylases (HDAC1–3) are histone lysine delactylases
10.1126/sciadv.abi6696 · 2022 · External reference
Lysine L-lactylation is the dominant lactylation isomer induced by glycolysis
10.1038/s41589-024-01680-8 · 2025 · External reference
HBO1 catalyzes lysine lactylation and mediates histone H3K9la to regulate gene transcription
10.1038/s41467-024-47900-6 · 2024 · External reference
High lactate levels predict likelihood of metastases, tumor recurrence, and restricted patient survival in human cervical cancers
2000 · External reference
The first demonstration of lactic acid in human blood in shock by Johann Joseph Scherer (1814–1869) in January 1843
10.1007/s00134-007-0788-7 · 2007 · External reference
Mechanisms of metabolism-coupled protein modifications
10.1038/s41589-024-01805-z · 2025 · External reference
Histone lactylation: a new role for glucose metabolism
10.1016/j.tibs.2019.12.004 · 2020 · External reference
Lactate promotes macrophage HMGB1 lactylation, acetylation, and exosomal release in polymicrobial sepsis
10.1038/s41418-021-00841-9 · 2022 · External reference
Nucleolin lactylation contributes to intrahepatic cholangiocarcinoma pathogenesis via RNA splicing regulation of MADD
10.1016/j.jhep.2024.04.010 · 2024 · External reference
Lactylation stabilizes TFEB to elevate autophagy and lysosomal activity
10.1083/jcb.202308099 · 2024 · External reference
KAT8-catalyzed lactylation promotes eEF1A2-mediated protein synthesis and colorectal carcinogenesis
10.1073/pnas.2314128121 · 2024 · External reference
Lactylation at lysine 145 fosters KAT8-TIP60 complex formation to promote p53 acetylation at lysine 120 and its pro-apoptotic function
2026 · External reference
Lactylation-driven nuclear RIG-I promoted by lactate transporter inhibitor suppresses DNA damage repair through inhibiting PARP1 activity
10.1016/j.celrep.2025.116854 · 2026 · External reference
RHOA lactylation at oncogenic hotspots promotes oncogenic activity and protein stabilization
10.1186/s12943-025-02511-7 · 2025 · External reference
NBS1 lactylation is required for efficient DNA repair and chemotherapy resistance
10.1038/s41586-024-07620-9 · 2024 · External reference
AARS1 and AARS2 sense L-lactate to regulate cGAS as global lysine lactyltransferases
10.1038/s41586-024-07992-y · 2024 · External reference
Lactylation in cancer: molecular mechanisms and advances in clinical study
2026 · External reference
The alanyl-tRNA synthetase AARS1 moonlights as a lactyltransferase to promote YAP signaling in gastric cancer
10.1172/jci174587 · 2024 · External reference
Lactylation stabilizes PD-L1 to promote tumor immune evasion and cell growth
10.1038/s41419-026-08589-1 · 2026 · External reference
Hypoxia induces mitochondrial protein lactylation to limit oxidative phosphorylation
10.1038/s41422-023-00864-6 · 2024 · External reference
YiaC and CobB regulate lysine lactylation in Escherichia coli
10.1038/s41467-022-34399-y · 2022 · External reference
Recent advances of lysine lactylation in prokaryotes and eukaryotes
10.3389/fmolb.2024.1510975 · 2025 · External reference
Lysine lactylation regulates metabolic pathways and biofilm formation in Streptococcus mutans
10.1126/scisignal.adg1849 · 2023 · External reference
Sirtuin 1/sirtuin 3 are robust lysine delactylases and sirtuin 1-mediated delactylation regulates glycolysis
10.1016/j.isci.2024.110911 · 2024 · External reference
Class I histone deacetylases catalyze lysine lactylation
10.1016/j.jbc.2025.110602 · 2025 · External reference
A role for HDAC3 in regulating histone lactylation and maintaining oocyte chromatin architecture and fertility
2026 · External reference
ASH2L‐K312‐Lac stimulates angiogenesis in tumors to expedite the malignant progression of hepatocellular carcinoma
10.1002/advs.202509477 · 2025 · External reference
Hypoxia‐Induced PRMT1 Lactylation Drives Vimentin Arginine Asymmetric Dimethylation in Tumor Metastasis
10.1002/advs.202509861 · 2025 · External reference
Lactylation of PTBP1 drives a pro-apoptotic positive feedback loop in microglia following oxygen-glucose deprivation/reoxygenation-induced injury
2026 · External reference
10.15252/embr.202256052
10.15252/embr.202256052 · External reference
Lactylation of RNA m6A demethylase ALKBH5 promotes innate immune response to DNA herpesviruses and mpox virus
10.1073/pnas.2409132121 · 2024 · External reference
10.1016/j.redox.2025.103869
10.1016/j.redox.2025.103869 · External reference
PARK7-Mediated Delactylation of SF3B Reprograms RNA Splicing to Attenuate Fibrosis and Promote Antitumor Immunity
10.1158/0008-5472.can-25-5662 · 2026 · External reference
Dux activates metabolism-lactylation-MET network during early iPSC reprogramming with Brg1 as the histone lactylation reader
10.1093/nar/gkae183 · 2024 · External reference
The TRIM33 bromodomain recognizes histone lysine lactylation
10.1021/acschembio.4c00248 · 2024 · External reference
DPF2 reads histone lactylation to drive transcription and tumorigenesis
10.1073/pnas.2421496121 · 2024 · External reference
BRD9 recognizes lactate-induced H3K18 lactylation to drive oncogenic chromatin remodeling in hepatocellular carcinoma
2026 · External reference
10.1016/j.cmet.2023.06.013
10.1016/j.cmet.2023.06.013 · External reference
Metabolic regulation of cytoskeleton functions by HDAC6-catalyzed α-tubulin lactylation
10.1038/s41467-024-52729-0 · 2024 · External reference
α-Tubulin K40 acetylation is required for contact inhibition of proliferation and cell–substrate adhesion
10.1091/mbc.e13-10-0609 · 2014 · External reference
10.1016/j.cell.2024.04.002
10.1016/j.cell.2024.04.002 · External reference
Acetylation of the p53 DNA-binding domain regulates apoptosis induction
10.1016/j.molcel.2006.11.026 · 2006 · External reference
Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma
10.1038/s42255-022-00710-w · 2023 · External reference
Integrated lactylome characterization reveals the molecular dynamics of protein regulation in gastrointestinal cancers
10.1002/advs.202400227 · 2024 · External reference
Lactylome analysis unveils lactylation‐dependent mechanisms of stemness remodeling in the liver cancer stem cells
10.1002/advs.202405975 · 2024 · External reference
Cyclic immonium ion of lactyllysine reveals widespread lactylation in the human proteome
10.1038/s41592-022-01523-1 · 2022 · External reference
Genetic code expansion reveals site-specific lactylation in living cells reshapes protein functions
10.1038/s41467-024-55165-2 · 2025 · External reference
Hypoxia induced β-catenin lactylation promotes the cell proliferation and stemness of colorectal cancer through the wnt signaling pathway
10.1016/j.yexcr.2022.113439 · 2023 · External reference
Dynamic investigation of hypoxia-induced L-lactylation
10.1073/pnas.2404899122 · 2025 · External reference
Lactylation modification of HIF-1α enhances its stability by blocking VHL recognition
10.1186/s12964-025-02366-x · 2025 · External reference
PFKP lactylation promotes the ovarian cancer progression through targeting PTEN
10.1007/s10528-024-10990-4 · 2025 · External reference
Proteomic analysis identifies PFKP lactylation in SW480 colon cancer cells
10.1016/j.isci.2023.108645 · 2024 · External reference
Identification of protein lysine lactylation and potential targets in esophageal squamous cell carcinoma
10.21037/tcr-2025-1-2204 · 2026 · External reference
The lactate‐primed KAT8‒PCK2 axis exacerbates hepatic ferroptosis during ischemia/reperfusion injury by reprogramming OXSM‐dependent mitochondrial fatty acid synthesis
10.1002/advs.202414141 · 2025 · External reference
Targeting metabolic plasticity and flexibility dynamics for cancer therapy
10.1158/2159-8290.cd-20-0844 · 2020 · External reference
Lactic acid promotes metastasis of papillary thyroid carcinoma by enhancing CPT1A lactylation
2026 · External reference
H4K79 and H4K91 histone lactylation, newly identified lactylation sites enriched in breast cancer
10.1186/s13046-025-03512-6 · 2025 · External reference
ABCF1-K430-Lactylation promotes HCC malignant progression via transcriptional activation of HIF1 signaling pathway
10.1038/s41418-024-01436-w · 2025 · External reference
A ESRP1/circPHGDH/miR-149/RAP1B positive feedback loop promotes the malignant behaviors and glycolysis of prostate cancer cell
10.1038/s12276-026-01646-x · 2026 · External reference
NUSAP1-LDHA-Glycolysis-Lactate feedforward loop promotes Warburg effect and metastasis in pancreatic ductal adenocarcinoma
10.1016/j.canlet.2023.216285 · 2023 · External reference
K90 lactylation orchestrates YAP nuclear sequestration by impairing binding with exportin CRM1 and enhances HCC malignancy
10.1016/j.canlet.2024.217386 · 2025 · External reference
Lactylation of HK2 facilitates cisplatin resistance in NSCLC by promoting cell migration, invasion, and glycolysis
2025 · External reference
Oxidative stress regulates the catalytic activity and mitochondrial localization of HK2 in trophoblast by regulating K346 lactylation
10.1096/fj.202402430rr · 2025 · External reference
YY1 lactylation in microglia promotes angiogenesis through transcription activation-mediated upregulation of FGF2
10.1186/s13059-023-02931-y · 2023 · External reference
Lactylation-driven transcriptional activation of FBXO33 promotes gallbladder cancer metastasis by regulating p53 polyubiquitination
10.1038/s41419-025-07372-y · 2025 · External reference
Epithelial mesenchymal transition in tumor metastasis
10.1146/annurev-pathol-020117-043854 · 2018 · External reference
Epithelial–mesenchymal transition: the history, regulatory mechanism, and cancer therapeutic opportunities
10.1002/mco2.144 · 2022 · External reference
Lactate metabolism and lactylation in cancer: from pathogenesis to therapeutic advances
10.1038/s41392-026-02672-x · 2026 · External reference
Lactate-induced activation of tumor-associated fibroblasts and IL-8-mediated macrophage recruitment promote lung cancer progression
10.1016/j.redox.2024.103209 · 2024 · External reference
Lactylation in cancer: mechanistic insights, tumor microenvironment, and therapeutic horizons
10.3389/fimmu.2025.1697428 · 2025 · External reference
10.1016/j.cmet.2024.07.011
10.1016/j.cmet.2024.07.011 · External reference
HAT1 functions as a lactyltransferase and mediates RPA1 lactylation to promote DNA repair and radioresistance in lung adenocarcinoma
10.1038/s41419-025-08113-x · 2025 · External reference
EP300‐Mediated MTF1‐K218 Lactylation Buffers AR‐Driven Copper Overload to Suppress Cuproptosis in Castration‐Resistant Prostate Cancer
2026 · External reference
LDHA facilitates immune escape in bladder cancer through H4K5 lactylation-dependent upregulation of PD-L1
2025 · External reference
Lactylation of PD-L1 by a lactyltransferase HAT1 dictates its protein stability and tumor immune evasion
10.1073/pnas.2537490123 · 2026 · External reference
10.1016/j.cmet.2024.10.019
10.1016/j.cmet.2024.10.019 · External reference
HMGB1 lactylation drives neutrophil extracellular trap formation in lactate-induced acute kidney injury
10.3389/fimmu.2024.1475543 · 2025 · External reference
Lactylated apolipoprotein C‐II induces immunotherapy resistance by promoting extracellular lipolysis
10.1002/advs.202470226 · 2024 · External reference
Lactate Dehydrogenase B delactylation promotes gastric cancer metastasis via enhancing glutathione-mediated resistance to ferroptosis
10.1007/s10565-026-10165-4 · 2026 · External reference
10.1016/j.chembiol.2026.01.003
10.1016/j.chembiol.2026.01.003 · External reference
Lactylation stabilizes DCBLD1 activating the pentose phosphate pathway to promote cervical cancer progression
10.1186/s13046-024-02943-x · 2024 · External reference
Aldolase B-driven lactagenesis and CEACAM6 activation promote cell renewal and chemoresistance in colorectal cancer through the Warburg effect
10.1038/s41419-023-06187-z · 2023 · External reference
10.1016/j.molcel.2022.02.033
10.1016/j.molcel.2022.02.033 · External reference
New insights into the regulation of METTL3 and its role in tumors
10.1186/s12964-023-01360-5 · 2023 · External reference
Histone lactylation drives METTL3 upregulation-mediated RNA m6A modification of CCT2 to hinder CD8+ T cell survival in gastric cancer
10.1007/s00018-025-05955-8 · 2025 · External reference
Crosstalk between lactylation and RNA modifications in tumorigenesis: mechanisms and therapeutic implications
10.1186/s40364-025-00824-9 · 2025 · External reference
Lactylation of METTL16 promotes cuproptosis via m6A-modification on FDX1 mRNA in gastric cancer
10.1038/s41467-023-42025-8 · 2023 · External reference
NSUN2 lactylation drives cancer cell resistance to ferroptosis through enhancing GCLC-dependent glutathione synthesis
10.1016/j.redox.2024.103479 · 2025 · External reference
Lactylation-driven NSUN2-mediated RNA m5C modification promotes perineural invasion in pancreatic cancer
10.7150/thno.122294 · 2026 · External reference
Tufm lactylation regulates neuronal apoptosis by modulating mitophagy in traumatic brain injury
10.1038/s41418-024-01408-0 · 2025 · External reference
Lactate enhances NMNAT1 lactylation to sustain nuclear NAD+ salvage pathway and promote survival of pancreatic adenocarcinoma cells under glucose-deprived conditions
10.1016/j.canlet.2024.216806 · 2024 · External reference
Lactate dehydrogenase A–mediated CREB1 lactylation promotes breast cancer brain metastasis by transcriptionally activating cytoskeletal remodeling
10.1093/neuonc/noag114 · 2026 · External reference
Integrated multi-omics reveals glycolytic gene signatures of lung adenocarcinoma brain metastasis and the impact of Rac2 lactylation on immunosuppressive microenvironment
10.1186/s12967-025-07207-6 · 2025 · External reference
SLC2A3‐Mediated Lactate Metabolism Promotes Lung Cancer Bone Metastasis by Modulating P53 Lactylation and Immune Evasion
2026 · External reference
Tumor-resident microbiota contributes to colorectal cancer liver metastasis by lactylation and immune modulation
10.1038/s41388-024-03080-7 · 2024 · External reference
Lactate accumulation drives hepatocellular carcinoma metastasis through facilitating tumor-derived exosome biogenesis by Rab7A lactylation
10.1016/j.canlet.2025.217636 · 2025 · External reference
Suppression of tumor aggression through metabolic reprogramming via oxamate targeting LDHA
10.3390/ijms27073245 · 2026 · External reference
Repurposing an antiepileptic drug for the treatment of glioblastoma
10.1007/s11095-022-03399-4 · 2022 · External reference
Lactic acid inhibits the interaction between PD-L1 protein and PD-L1 antibody in the PD-1/PD-L1 blockade therapy-resistant tumor
10.1016/j.ymthe.2024.12.044 · 2025 · External reference
Effects of lactate transport inhibition by AZD3965 in muscle-invasive urothelial bladder cancer
10.3390/pharmaceutics15122688 · 2023 · External reference
Pre-clinical pharmacology of AZD3965, a selective inhibitor of MCT1: DLBCL, NHL and Burkitt’s lymphoma anti-tumor activity
10.18632/oncotarget.18215 · 2017 · External reference
Pharmacologic LDH inhibition redirects intratumoral glucose uptake and improves antitumor immunity in solid tumor models
10.1172/jci177606 · 2024 · External reference
Global Profiling of Lysine Lactylation in Prostate Cancer Cells
10.21873/cgp.20547 · 2025 · External reference
Lactate signaling and immune suppression in tumors: Mechanisms and therapeutic implications
10.1007/s13402-026-01186-6 · 2026 · External reference
Pharmacologically targeting protein lactylation to overcome cancer drug resistance
10.1016/j.ejmech.2025.117905 · 2025 · External reference
10.2147/dddt.s567488
10.2147/dddt.s567488 · External reference
Targeting lactate and lactylation in cancer metabolism and immunotherapy
10.1002/advs.202515403 · 2026 · External reference
The clinical prognostic value of lactylation-regulated proteins in gastric cancer
10.1021/acs.jproteome.5c00813 · 2026 · External reference
Protein lactylation within the nucleus independently predicts the prognosis of non‑specific triple‑negative breast cancer
10.3892/ol.2024.14818 · 2024 · External reference
A lactylation-related gene signature predicts metastasis and prognosis in breast cancer
10.1038/s41598-025-26165-z · 2025 · External reference
Constructing lactylation-related genes prognostic model to effectively predict the disease-free survival and treatment responsiveness in prostate cancer based on machine learning
10.3389/fgene.2024.1343140 · 2024 · External reference
