Research progress on the interaction between glucose metabolic reprogramming and lactylation in tumors

Area of Science:

• Biochemistry
• Molecular Biology
• Cancer Research

Background:

• Glucose metabolic reprogramming alters cellular metabolism for rapid ATP production, even in oxygen-rich conditions.
• This process leads to lactate accumulation, affecting tumor and immune cells within the tumor microenvironment (TME).
• Lactylation, a post-translational modification, arises from lactate accumulation and impacts protein function and gene expression.

Purpose of the Study:

• To review the mechanisms of lactylation and glucose metabolic reprogramming.
• To explore their impact on immune cells within the TME.
• To elucidate their interrelations in tumor progression, immunity, and inflammation.

Main Methods:

• Review of existing literature on glucose metabolism, lactylation, and cancer immunology.
• Analysis of the molecular pathways linking glucose metabolism, lactate production, and epigenetic modifications.
• Examination of the effects of lactylation on immune cell function and the tumor microenvironment.

Main Results:

• Glucose reprogramming activates key enzymes (HK2, PKM2, LDHA) via transcription factors (HIF-1α, c-Myc), boosting glycolysis and lactate.
• Lactate serves as a substrate for lactylation, mediated by enzymes like CBP/p300, altering protein function and gene expression.
• Lactylation inhibits anti-tumor immunity by upregulating oncogenic pathways, promoting M2 macrophage polarization, and causing T-cell dysfunction.

Conclusions:

• Glucose metabolic reprogramming and lactylation are interconnected, driving tumorigenesis by affecting gene expression, protein function, and the TME.
• These processes contribute to immune evasion and cancer progression.
• Understanding these mechanisms offers potential therapeutic targets for cancer treatment.