Lactate and lactylation in cancer

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Фев. 11, 2025

Abstract Accumulated evidence has implicated the diverse and substantial influence of lactate on cellular differentiation fate regulation in physiological pathological settings, particularly intricate conditions such as cancer. Specifically, been demonstrated to be pivotal molding tumor microenvironment (TME) through its effects different cell populations. Within cells, impacts signaling pathways, augments shuttle process, boosts resistance oxidative stress, contributes lactylation. In various populations, interplay between immune cells governs processes differentiation, response, surveillance, treatment effectiveness. Furthermore, communication stromal/endothelial supports basal membrane (BM) remodeling, epithelial-mesenchymal transitions (EMT), metabolic reprogramming, angiogenesis, drug resistance. Focusing production transport, specifically dehydrogenase (LDH) monocarboxylate transporters (MCT), shown promise Inhibitors targeting LDH MCT act both suppressors enhancers immunotherapy, leading a synergistic therapeutic effect when combined with immunotherapy. The review underscores importance progression provides valuable perspectives potential approaches that target vulnerability metabolism, highlighting Heel Achilles for cancer treatment.

Язык: Английский

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Lactylation: The emerging frontier in post-translational modification

Frontiers in Genetics, Год журнала: 2024, Номер 15

Опубликована: Июнь 27, 2024

Lactate, a metabolic byproduct, has gained recognition as highly influential signaling molecule. Lactylation, an emerging form of post-translational modification derived from lactate, plays crucial role in numerous cellular processes such inflammation, embryonic development, tumor proliferation, and metabolism. However, the precise molecular mechanisms through which lactylation governs these biological functions both physiological pathological contexts remain elusive. Hence, it is imperative to provide comprehensive overview order elucidate its significance establish foundation for forthcoming investigations. This review aims succinctly outline process characterization protein across diverse organisms. Additionally, A summary regulatory specific diseases presented. Finally, this concludes by delineating existing research gaps proposing primary directions future

Язык: Английский

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Glutathione and a Pool of Metabolites Partly Related to Oxidative Stress Are Associated with Low and High Myopia in an Altered Bioenergetic Environment

Antioxidants, Год журнала: 2024, Номер 13(5), С. 539 - 539

Опубликована: Апрель 27, 2024

Oxidative stress forms part of the molecular basis contributing to development and manifestation myopia, a refractive error with associated pathology that is increasingly prevalent worldwide subsequently leads an upsurge in degenerative visual impairment due conditions are especially high myopia. The purpose our study was examine interrelation potential oxidative-stress-related metabolites found aqueous humor high-myopic, low-myopic, non-myopic patients within clinical study. We conducted cross-sectional study, selecting two sets undergoing cataract surgery. first set, which used analyze through NMR assay, comprised 116 patients. A total 59 were assigned quantified. PLS-DA score plot clearly showed separation minimal overlap between HM control samples. model allowed us determine 31 major metabolite differences groups. Complementary statistical analysis data six presented significant among experimental groups (p < 005). number these discovered have direct or indirect connection oxidative linked myopic eyes. Notably, we identified bioenergetic pathways undergone methylation, along choline its derivatives. second set consisted 73 who underwent glutathione assay. Here, variations both reduced oxidized all patient 0.01) for time. Axial length, status, complete ophthalmologic examination also recorded, interrelations metabolic parameters evaluated.

Язык: Английский

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Lactate/lactylation in ocular development and diseases

Trends in Molecular Medicine, Год журнала: 2024, Номер unknown

Опубликована: Июль 1, 2024

Язык: Английский

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Lactate and Lysine Lactylation of Histone Regulate Transcription in Cancer

Heliyon, Год журнала: 2024, Номер 10(21), С. e38426 - e38426

Опубликована: Окт. 1, 2024

Язык: Английский

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PKM2‐Driven Lactate Overproduction Triggers Endothelial‐To‐Mesenchymal Transition in Ischemic Flap via Mediating TWIST1 Lactylation

Advanced Science, Год журнала: 2024, Номер unknown

Опубликована: Окт. 30, 2024

Abstract The accumulation of lactate is a rising risk factor for patients after flap transplantation. Endothelial‐to‐mesenchymal transition (EndoMT) plays critical role in skin fibrosis. Nevertheless, whether overproduction directly contributes to necrosis and its mechanism remain unknown. current study reveals that mice exhibit enhanced PKM2 fibrotic response. Endothelial‐specific deletion attenuates ameliorates fibrosis mice. Administration or overexpressing promotes dysfunction endothelial cells stimulates mesenchymal‐like phenotype following hypoxia. Mechanistically, glycolytic‐lactate induces correlation between Twist1 p300/CBP, leading lactylation lysine 150 (K150la). increase K150la phosphorylation nuclear translocation further regulates the transcription TGFB1 , hence inducing phenotype. Genetically endothelial‐specific diminishes lactylation, then EndoMT‐associated ischemia. serum levels transplantation are elevated predictive value prognosis. This findings suggested novel PKM2‐derived mediating exacerbates Inhibition reduces response might become potential therapeutic strategy

Язык: Английский

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Histone lactylation mediated by Fam172a in POMC neurons regulates energy balance

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Ноя. 22, 2024

Glycolysis-derived lactate was identified as substrate for histone lactylation, which has been regarded a significant role in transcriptional regulation many tissues. However, the of lactylation metabolic center, hypothalamus, is still unknown. Here, we show that hypothalamic pro-opiomelanocortin (POMC) neuron-specific deletion family with sequence similarity 172, member A (Fam172a) can increase and protect mice against diet-induced obesity (DIO) related disorders. Conversely, overexpression Fam172a POMC neurons led to an obesity-like phenotype. Using RNA-seq CUT&Tag chromatin profiling analyzes, find knockdown activates glycolytic process increases peptidylglycine α-amidating monooxygenase (PAM), affects synthesis α-MSH, via H4K12la (histone lactylation). In addition, pharmacological inhibition production clearly abrogates anti-obesity effect PFKO (POMC-Cre, Fam172aloxP/loxP, knockout). These findings highlight importance development our results mainly concern male mice. reported play regulation. it's hypothalamus authors disorders

Язык: Английский

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An Evidence-Based Narrative Review of Scleral Hypoxia Theory in Myopia: From Mechanisms to Treatments

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(1), С. 332 - 332

Опубликована: Янв. 2, 2025

Myopia is one of the dominant causes visual impairment in world. Pathological myopia could even lead to other serious eye diseases. Researchers have reached a consensus that be caused by both environmental and genetic risk factors. Exploring pathological mechanism can provide scientific basis for developing measures delay progression or treat it. Recent advances highlight scleral hypoxia an important factor promoting myopia. In this review, we summarized role pathology also provided interventions target directly indirectly. We hope review will aid development novel therapeutic strategies drugs

Язык: Английский

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Lgals3 Promotes Calcium Oxalate Crystal Formation and Kidney Injury Through Histone Lactylation‐Mediated FGFR4 Activation

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Фев. 4, 2025

Abstract The incidence of kidney stones is increasing worldwide. However, the underlying mechanism process stone formation and damage caused are not well understood. Here, it observed that Lgals3, a β‐galactoside‐binding protein, significantly increased in tissues with calcium oxalate (CaOx) stones, both vivo vitro models. Lgals3 expression positively correlated deposition CaOx crystals. Knockout markedly reduces crystal renal fibrosis vivo. Furthermore, deficiency decrease glycolytic rate lactate production during inhibited histone lactylation H3K18la. Mechanistic studies shows directly interacted key glycolysis protein pyruvate kinase M2 (PKM2) promoted its by modulating E3 ligase Trim21, preventing ubiquitination PKM2. H3K18 injury vitro. inhibites transcription, activation, FGFR4 through inhibition These findings suggest may play role interacting PKM2 promoting H3K18la‐mediated gene transcription activation.

Язык: Английский

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EFEMP1-Mediated Regulation of Choroidal Vascular Dysfunction in Myopia: Insights Into the FOXO3/VEGFA Pathway as a Therapeutic Target

Investigative Ophthalmology & Visual Science, Год журнала: 2025, Номер 66(3), С. 43 - 43

Опубликована: Март 20, 2025

Purpose: This study investigates the role of EFEMP1 in choroidal vascular dysfunction and its implications for myopia progression, specifically focusing on FOXO3/VEGFA signaling pathway as a potential therapeutic target. Methods: We utilized adeno-associated virus (AAV) to overexpress knock down choroid guinea pigs. Subsequent proteomic analyses were conducted tissue. used Gene Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) identify relevant pathways genes. In vitro experiments performed RF/6A cells, where both FOXO3 underwent overexpression knockdown. series cell culture experiments, including assessments proliferation, migration, tube formation, sprouting assays, evaluate functional effects EFEMP1. Quantitative reverse transcription PCR Western blot measure gene protein expression levels. Results: Silencing significantly reduced slowed progression myopia. Proteomic analysis demonstrated that regulates activity, resulting increased VEGFA cells promoting angiogenesis. Conversely, knockdown led decreased levels, confirming modulates through FOXO3. Conclusions: Targeting may offer novel strategy prevention treatment by alleviating associated dysregulation. Further exploration could provide additional insights into interventions

Язык: Английский

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