Nature Metabolism, Journal Year: 2025, Volume and Issue: unknown
Published: April 2, 2025
Language: Английский
Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)
Published: Feb. 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.
Language: Английский
Citations
9
Advanced Science, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 14, 2025
Abstract The current treatment of triple‐negative breast cancer (TNBC) is still primarily based on platinum‐based chemotherapy. However, TNBC cells frequently develop resistance to platinum and experience relapse after drug withdrawal. It crucial specifically target eliminate cisplatin‐tolerant administration. Here, it reported that upregulated N 6 ‐methyladenosine (m A) modification drives the development in during cisplatin treatment. Mechanistically, histone deacetylase 2 (HDAC2) mediates delactylation methyltransferase‐like 3 (METTL3), facilitating METTL3 interaction with Wilms’‐tumor‐1‐associated protein subsequently increasing m A transcript‐associated DNA damage repair. This ultimately promotes cell survival under cisplatin. Furthermore, pharmacological inhibition HDAC2 using Tucidinostat can enhance sensitivity therapy. study not only elucidates biological function lactylated tumor but also highlights its negative regulatory effect resistance. Additionally, underscores nonclassical functional mechanism as a HDAC inhibitor for improving efficacy against TNBC.
Language: Английский
Citations
2
Cell Metabolism, Journal Year: 2024, Volume and Issue: 36(8), P. 1637 - 1639
Published: Aug. 1, 2024
Language: Английский
Citations
9
Journal of Experimental & Clinical Cancer Research, Journal Year: 2025, Volume and Issue: 44(1)
Published: Jan. 3, 2025
Language: Английский
Citations
1
Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13
Published: Jan. 24, 2025
Lactylation, a newly discovered protein posttranslational modification (PTM) in 2019, primarily occurs on lysine residues. Lactylation of histones was initially identified, and subsequent studies have increasingly demonstrated its widespread presence non-histone proteins. Recently, high-throughput proteomics identified large number lactylated proteins sites, revealing their global regulatory role disease development. Notably, this is catalyzed by lactyltransferase reversed delactylase, with numerous new enzymes, such as AARS1/2, reported to be involved. Specifically, these revealed how lactylation exerts influence through alterations spatial conformation, molecular interactions, enzyme activity subcellular localization. Indeed, implicated various physiological pathological processes, including tumor development, cardiovascular cerebrovascular diseases, immune cell activation psychiatric disorders. This review provides the latest advancements research roles lactylation, highlighting crucial scientific importance for future studies.
Language: Английский
Citations
1
Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(7)
Published: Feb. 10, 2025
Male germ cells, which are responsible for producing millions of genetically diverse sperm through meiosis in the testis, rely on lactate as their central energy metabolite. Recent study has revealed that induces epigenetic modification cells histone lysine lactylation. Here, we report dynamic lactylation at H4-lysine 5 (K5), -K8, and -K12 during prophase I mouse spermatogenesis. By profiling genome-wide occupancy H4-K8 (H4K8la), peaks zygotene, our data show H4K8la mark is observed promoters genes exhibiting active expression with Gene Ontology functions enriched meiosis. Notably, also demonstrate closely associated recombination hotspots, where machinery involved processing DNA double-stranded breaks, such SPO11, DMC1, RAD51, RPA2, engaged. In addition, was detected meiosis-specific cohesion sites (marked by RAD21L REC8) flanking hotspots. Functionally, upregulation key meiotic modifications. Additionally, shows colocalization interaction PRDM9 Finally, HBO1, a lactyltransferase, highly expressed cells. vitro assays reveal HBO1 H4K8la, pharmacological inhibition mice reduces levels disrupts Collectively, findings suggest serves an mechanism gene male
Language: Английский
Citations
1
Advanced Science, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 14, 2025
Lactate derived from aerobic glycolysis is crucial for DNA damage repair and chemoresistance. Nevertheless, it frequently noted that cancer cells depend on glutaminolysis to replenish essential metabolites. Whether how might enhance lactate production facilitate in remains unknown. Here, shown malate enzyme 2 (ME2), which metabolizes glutamine-derived pyruvate, contributes chemotherapy resistance ovarian cancer. Mechanistically, reduces the expression of glucose transporters impairs uptake cells. The resultant decrease intracellular levels triggers acetylation ME2 at lysine 156 by ACAT1, turn potentiates activity facilitates glutamine. ME2-derived development acquired chemoresistance subjected prolonged chemotherapy, primarily facilitating lactylation proteins involved homologous recombination repair. Targeting ACAT1 inhibit effectively reduced both vitro vivo models. These findings underscore significance acetylated ME2-mediated glutamine chemoresistance, particularly under conditions within cell, thereby complementing Warburg effect offering new perspectives metabolic links resistance.
Language: Английский
Citations
1
Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)
Published: Feb. 20, 2025
Recent progress in cancer metabolism research has identified lactylation as a critical post-translational modification influencing tumor development and progression. The process relies on lactate accumulation the activation of lactate-sensitive acyltransferases. Beyond its role epigenetic regulation, emerged significant factor evolution, offering fresh opportunities for developing targeted therapies that transcend traditional approaches. This review explores growing importance biology highlights potential advancing diagnostic tools therapeutic strategies.
Language: Английский
Citations
1
Clinical and Translational Medicine, Journal Year: 2024, Volume and Issue: 14(11)
Published: Oct. 25, 2024
Lactylation, a recently identified form of protein post-translational modification (PTM), has emerged as key player in cancer biology. The Warburg effect, hallmark tumour metabolism, underscores the significance lactylation progression. By regulating gene transcription and function, facilitates metabolic reprogramming, enabling tumours to adapt nutrient limitations sustain rapid growth. Over past decade, extensive research revealed intricate regulatory network underlying tumours. Large-scale sequencing machine learning have confirmed widespread occurrence sites across proteome. Targeting enzymes or pathways demonstrated promising anti-tumour effects, highlighting therapeutic potential this modification. This review comprehensively explores mechanisms cells microenvironment. We expound on application advanced omics technologies for target identification data modelling within field. Additionally, we summarise existing anti-lactylation drugs discuss their clinical implications. providing comprehensive overview recent advancements, aims stimulate innovative accelerate translation lactylation-based therapies into practice. KEY POINTS: Lactylation significantly influences metabolism regulation, contributing Advanced reveal shows promise enhancing drug efficacy overcoming chemotherapy resistance. outlines implications future directions oncology.
Language: Английский
Citations
5
Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 179, P. 117420 - 117420
Published: Sept. 9, 2024
Language: Английский
Citations
4