Lactate and lactylation: metabolic architects of tumor progression and metastasis

Lactate and its associated modification, lactylation, have emerged as key regulators in influencing various cellular processes. This review explores the multifaceted roles of lactate and lactylation, highlighting their involvement in metabolic reprogramming and the modulation of key signaling pathways. Lactate and lactylation influence cell adhesion, protein degradation, and angiogenesis, contributing to tumor invasion and metastasis. These metabolic alterations maintain cancer stem cell characteristics, support tumorigenesis and resistance to therapy. Lactate and lactylation also facilitate immune evasion in the tumor microenvironment (TME) by modulating immune cell function and immune checkpoint pathways. The complex interplay between lactate, lactylation, and various cellular and immune mechanisms underscores the potential of targeting lactate-related pathways as a therapeutic strategy for cancer treatment. Herein, we provide a comprehensive overview of the current understanding of lactate and lactylation in cancer, offering insights into their roles as key drivers of tumor progression and metastasis.