Lactylation in cancer: a new frontier in metabolic-epigenetic regulation and clinical practice.
5 affiliations
- 1Department of Pathology, School of Basic Medical Sciences, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin, 150081, China.
- 2Department of Oncology, Chifeng City Hospital, Chifeng, 024000, China.
- 3Cardiovascular Center, Inner Mongolia People's Hospital, Hohhot, 010017, Inner Mongolia, China. [email protected].
- 4Department of Oncology, Chifeng City Hospital, Chifeng, 024000, China. [email protected].
- 5Department of Pathology, School of Basic Medical Sciences, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin, 150081, China. [email protected].
Abstract
The discovery of lysine lactylation (Kla) redefines lactate from a passive glycolytic by-product into a bioactive metabolic mediator that directly links cellular metabolism to epigenetic regulation. This emerging post-translational modification dynamically alters histone and non-histone proteins, thereby reconfiguring gene expression programs and immune responses within the tumor microenvironment (TME). It consequently promotes core malignant phenotypes including uncontrolled proliferation, epithelial-mesenchymal transition (EMT), metastatic dissemination, and resistance to chemotherapy, radiotherapy, and immune checkpoint blockade. Specific epigenetic signatures, notably histone H3K18la and H4K12la marks, serve as transcriptional anchors for oncogenic pathways across multiple cancer types. Multi-omics analyses have further yielded Kla-associated gene profiles with the potential to refine prognostic stratification and drug-target identification. These findings establish Kla as a central axis in tumor-associated metabolic-epigenetic crosstalk. Effective clinical application of KLAsKla biomarkers requires resolving technical detection limits and addressing the spatiotemporal heterogeneity that currently constrains machine learning-based prognostic models. Overcoming these bottlenecks is contingent upon leveraging advanced technologies such as single-cell multi-omics and spatial transcriptomics. This review characterizes the emerging roles of Kla in tumor metabolism, providing a framework for its future application as a diagnostic and therapeutic cornerstone in precision oncology.
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BibTeX
@article{zhang2026lactylation,
title = {{Lactylation in cancer: a new frontier in metabolic-epigenetic regulation and clinical practice.}},
author = {Yihan Zhang and Lan Chen and Yaxi Qin and Ying Wang and Xi Liu and Minghui Zhang and Jing Tang},
journal = {Cell communication and signaling : CCS},
year = {2026},
month = jul,
doi = {10.1186/s12964-026-03085-7},
url = {https://europepmc.org/article/MED/42897554},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Lactylation in cancer: a new frontier in metabolic-epigenetic regulation and clinical practice.
AU - Yihan Zhang
AU - Lan Chen
AU - Yaxi Qin
AU - Ying Wang
AU - Xi Liu
AU - Minghui Zhang
AU - Jing Tang
PY - 2026
DA - 2026/07/01
JO - Cell communication and signaling : CCS
DO - 10.1186/s12964-026-03085-7
UR - https://europepmc.org/article/MED/42897554
AB - The discovery of lysine lactylation (Kla) redefines lactate from a passive glycolytic by-product into a bioactive metabolic mediator that directly links cellular metabolism to epigenetic regulation. This emerging post-translational modification dynamically alters histone and non-histone proteins, thereby reconfiguring gene expression programs and immune responses within the tumor microenvironment (TME). It consequently promotes core malignant phenotypes including uncontrolled proliferation, epithelial-mesenchymal transition (EMT), metastatic dissemination, and resistance to chemotherapy, radiotherapy, and immune checkpoint blockade. Specific epigenetic signatures, notably histone H3K18la and H4K12la marks, serve as transcriptional anchors for oncogenic pathways across multiple cancer types. Multi-omics analyses have further yielded Kla-associated gene profiles with the potential to refine prognostic stratification and drug-target identification. These findings establish Kla as a central axis in tumor-associated metabolic-epigenetic crosstalk. Effective clinical application of KLAsKla biomarkers requires resolving technical detection limits and addressing the spatiotemporal heterogeneity that currently constrains machine learning-based prognostic models. Overcoming these bottlenecks is contingent upon leveraging advanced technologies such as single-cell multi-omics and spatial transcriptomics. This review characterizes the emerging roles of Kla in tumor metabolism, providing a framework for its future application as a diagnostic and therapeutic cornerstone in precision oncology.
SN - 1478-811X
ER -