Protein Lactylation in Cancer: Mechanisms and Therapeutic Targets

Area of Science:

• Biochemistry
• Molecular Biology
• Oncology

Background:

• Cancer cells exhibit the Warburg effect, increasing aerobic glycolysis and lactate production.
• Lactate fuels lysine lactylation (Kla), a posttranslational modification linking metabolism to epigenetic reprogramming.
• Kla influences histone and nonhistone proteins, driving cancer adaptation and progression.

Purpose of the Study:

• To review the multifactorial regulation of lactylation in cancer.
• To explore the translational potential of lactylation in overcoming tumor heterogeneity and resistance.
• To highlight lactylation's emerging roles in cancer therapies.

Main Methods:

• Literature review synthesizing current research on lactylation.
• Examination of regulatory factors influencing lactylation.
• Discussion of therapeutic strategies targeting lactylation.

Main Results:

• Lactylation plays diverse roles in cancer therapy, enhancing chemotherapy, stabilizing targeted therapy effectors, and modulating the tumor microenvironment (TME) in immunotherapy.
• Regulatory factors include competitive posttranslational modifications, genetic mutations, microbial influences, and environmental signals.
• Therapeutic targeting involves indirect modulators and visualization techniques.

Conclusions:

• Lactylation represents a reversible metabolic-epigenetic axis crucial for precision oncology.
• Targeting lactylation can lead to predictive biomarkers, combination therapies, and novel interventions for dynamic cancer challenges.