Protein lactylation in cancer: mechanisms and potential therapeutic implications

Increased glycolysis, which leads to high lactate production, is a common feature of cancer cells. Recent evidence suggests that lactate plays a role in the post-translational modification of histone and nonhistone proteins via lactylation. In contrast to genetic mutations, lactylation in cancer cells is reversible. Thus, reversing lactylation can be exploited as a pharmacological intervention for various cancers. Here we discuss recent advances in histone and nonhistone lactylation in cancer, including l-, d- and s-lactylation, as well as alanyl-tRNA synthetase as a novel lactyltransferase. We also discuss potential approaches for targeting lactylation as a therapeutic opportunity in cancer treatment. In the 1920s, Otto Warburg discovered that cancer cells use a lot of sugar even when oxygen is present. This process, called aerobic glycolysis, produces a substance called lactate. Scientists used to think lactate was just waste, but recent studies show it has important roles in cancer. Researchers found that lactate can change proteins in cells through a process called lactylation, which affects how genes are turned on or off. In this study, the authors explored how lactylation impacts cancer. They used various methods to study proteins and genes in cancer cells. They found that lactylation can change both histone proteins and nonhistone proteins, affecting gene expression and protein stability. This process can help cancer cells grow and resist treatment. The researchers concluded that targeting lactylation could be a new way to treat cancer. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.