Lactate-induced protein lactylation: A bridge between epigenetics and metabolic reprogramming in cancer

Lactate is not only an endpoint of glycolysis but is gradually being discovered to play the role of a universal metabolic fuel for energy via the 'lactate shuttle' moving between cells and transmitting signals. The glycolytic-dependent metabolism found in tumours and fast-growing cells has...

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Bibliographic Details
Published in:Cell proliferation 2023-10, Vol.56 (10), p.e13478-e13478
Main Authors: Wang, Ting, Ye, Zeng, Li, Zheng, Jing, De-Sheng, Fan, Gui-Xiong, Liu, Meng-Qi, Zhuo, Qi-Feng, Ji, Shun-Rong, Yu, Xian-Jun, Xu, Xiao-Wu, Qin, Yi
Format: Article
Language:English
Subjects:
Chromatin
Disease
DNA methylation
Energy
Energy metabolism
Epigenetics
Gene expression
Glycolysis
Histones
Immune system
Kinases
Lactic acid
Metabolism
Mutation
Pancreatic cancer
Proteins
Review
Reviews
Tumor microenvironment
Tumorigenesis
Tumors
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Summary:Lactate is not only an endpoint of glycolysis but is gradually being discovered to play the role of a universal metabolic fuel for energy via the 'lactate shuttle' moving between cells and transmitting signals. The glycolytic-dependent metabolism found in tumours and fast-growing cells has made lactate a pivotal player in energy metabolism reprogramming, which enables cells to obtain abundant energy in a short time. Moreover, lactate can provide favourable conditions for tumorigenesis by shaping the acidic tumour microenvironment, recruiting immune cells, etc. and the recently discovered lactate-induced lactylation moves even further on pro-tumorigenesis mechanisms of lactate production, circulation and utilization. As with other epigenetic modifications, lactylation can modify histone proteins to alter the spatial configuration of chromatin, affect DNA accessibility and regulate the expression of corresponding genes. What's more, the degree of lactylation is inseparable from the spatialized lactate concentration, which builds a bridge between epigenetics and metabolic reprogramming. Here, we review the important role of lactate in energy reprogramming, summarize the latest finding of lactylation in tumorigenesis and try to explore therapeutic strategies in oncotherapy that can kill two birds with one stone.
ISSN:0960-7722
1365-2184
DOI:10.1111/cpr.13478