Lactylation modification in cancer: mechanisms, functions, and therapeutic strategies

Experimental Hematology and Oncology, Год журнала: 2025, Номер 14(1)

Опубликована: Март 8, 2025

Cancer remains the leading cause of mortality worldwide, and emergence drug resistance has made identification new therapeutic targets imperative. Lactate, traditionally viewed as a byproduct glycolysis with limited ATP-producing capacity, recently gained recognition critical signaling molecule. It plays key role not only in cancer cell metabolism but also shaping tumor microenvironment (TME). Histone lysine lactylation, newly identified post-translational modification, been shown to influence range cellular processes cancer. Current research focuses on mechanisms functions histone lactylation cancer, including its gene expression regulation, signal transduction, protein synthesis. However, despite these advancements, there are still plenty barriers quest unravel modification. The single-cell spatial transcriptomics may offer valuable insights for selecting targets. This review provides comprehensive summary applications modification clinical settings. Through detailed analysis, we identify challenges limitations that exist current landscape. These lay groundwork future studies by highlighting promising directions.

Язык: Английский

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The role of protein lactylation: A kaleidoscopic post-translational modification in cancer

Molecular Cell, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

The recently discovered lysine lactylation represents a critical post-translational modification with widespread implications in epigenetics and cancer biology. Initially identified on histones, has been also described non-histone proteins, playing pivotal role transcriptional activation, protein function, cellular processes. Two major sources of the lactyl moiety have currently distinguished: L-lactyl-CoA (precursor L-lactyl moiety) S-D-lactylglutathione D-lactyl moiety), which enable enzymatic non-enzymatic mechanisms lactylation, respectively. Although specific writers, erasers, readers this are still unclear, acetyltransferases deacetylases proposed as crucial mediators lactylation. Remarkably, exerts significant influence cancer-related pathways, thereby shaping behavior during malignant transformation metastatic cascade. Hence, recent insights into underscore its growing potential tumor biology, targeting is emerging opportunity for treatment.

Язык: Английский

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Lactate: A key regulator of the immune response

Immunity, Год журнала: 2025, Номер 58(3), С. 535 - 554

Опубликована: Март 1, 2025

SummaryLactate, the end product of both anaerobic and aerobic glycolysis in proliferating growing cells—with latter process known as Warburg effect—is historically considered a mere waste cell tissue metabolism. However, research over past ten years has unveiled multifaceted functions lactate that critically shape impact cellular biology. Beyond serving fuel source, is now to influence gene expression through histone modification function signaling molecule impacts wide range activities. These properties have been particularly studied context adaptive innate immune responses. Here, we review diverse roles regulation system during homeostasis disease pathogenesis (including cancer, infection, cardiovascular diseases, autoimmunity). Furthermore, describe recently proposed therapeutic interventions for manipulating metabolism human diseases.

Язык: Английский

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L- and D-Lactate: unveiling their hidden functions in disease and health

Cell Communication and Signaling, Год журнала: 2025, Номер 23(1)

Опубликована: Март 12, 2025

Lactate, once considered a mere byproduct of anaerobic metabolism, is now recognized as critical signaling molecule with diverse roles in physiology and pathology. There are two stereoisomers lactate: L- D-lactate. Recent studies have shown that disruptions these lactate distinct effects on health disease. L-lactate central to glycolysis energy transfer through the Cori cycle but also acts dominant lactylation isomer induced by glycolysis, influencing metabolism cell survival. Although less studied, D-lactate linked metabolic disorders plays role mitochondrial dysfunction oxidative stress. This review focuses both examines their biosynthesis, transport, expanding physiological pathological processes, particularly functions cancer, immune regulation, inflammation, neurodegeneration other diseases. Finally, we assess therapeutic prospects targeting highlighting emerging strategies for intervention clinical settings. Our synthesizes current understanding D-lactate, offering insights into potential targets innovation.

Язык: Английский

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Turning sour into sweet: Lactylation modification as a promising target in cardiovascular health

Metabolism, Год журнала: 2025, Номер unknown, С. 156234 - 156234

Опубликована: Март 1, 2025

Язык: Английский

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