PROTEOMICS - CLINICAL APPLICATIONS, Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 28, 2024
The hippocampus has long been associated with cognition and memory function, the implications of lysine lactylation (Kla), a recently identified post-translational modification (PTM), in role remain largely unexplored.
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
3
Theranostics, Journal Year: 2025, Volume and Issue: 15(5), P. 1787 - 1821
Published: Jan. 2, 2025
Lactate is an indispensable substance in various cellular physiological functions and plays regulatory roles different aspects of energy metabolism signal transduction. Lactylation (Kla), a key pathway through which lactate exerts its functions, has been identified as novel posttranslational modification (PTM). Research indicates that Kla essential balancing mechanism variety organisms involved many biological processes pathways. closely related to disease development represents potential important new drug target. In line with existing reports, we searched for newly discovered sites on histone nonhistone proteins; reviewed the mechanisms (particularly focusing enzymes directly reversible regulation Kla, including "writers" (modifying enzymes), "readers" (modification-binding "erasers" (demodifying enzymes); summarized crosstalk between PTMs help researchers better understand widespread distribution diverse functions. Furthermore, considering "double-edged sword" role both pathological contexts, this review highlights "beneficial" states (energy metabolism, inflammatory responses, cell fate determination, development, etc.) "detrimental" pathogenic or inducive effects processes, particularly malignant tumors complex nontumor diseases. We also clarify molecular health disease, discuss feasibility therapeutic Finally, describe detection technologies their applications diagnosis clinical settings, aiming provide insights treatment diseases accelerate translation from laboratory research practice.
Language: Английский
Citations
2
Advanced Science, Journal Year: 2024, Volume and Issue: unknown
Published: July 17, 2024
Lysine lactylation (Kla) plays a vital role in several physiological processes. However, the cancer-specific modulation of Kla gastrointestinal (GI) tumors requires systematic elucidation. Here, global lactylome profiling cancerous and adjacent tissues is conducted from 40 patients with GI cancer identified 11698 sites. Lactylome integration revealed that affects proteins involved hallmark processes, including epigenetic rewiring, metabolic perturbations, genome instability. Moreover, study pan-cancer patterns alterations, among which 37 sites are consistently upregulated all four cancers gene regulation. It further verified CBX3 at K10 mediates its interaction marker H3K9me3 facilitates progression. Overall, this provides an invaluable resource for understanding landscape cancers, may provide new paths drug discovery these devastating diseases.
Language: Английский
Citations
10
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
7
Nature Cell Biology, Journal Year: 2025, Volume and Issue: unknown
Published: April 4, 2025
Language: Английский
Citations
0
Molecular Medicine, Journal Year: 2025, Volume and Issue: 31(1)
Published: April 22, 2025
Abstract In the clinical management of cancers, emergence chemoresistance represents a profound and imperative “pain point” that requires immediate attention. Understanding mechanisms is essential for developing effective therapeutic strategies. Importantly, existing studies have demonstrated glucose metabolic reprogramming, commonly referred to as Warburg effect or aerobic glycolysis, major contributor chemoresistance. Additionally, lactate, byproduct functions signaling molecule supports lysine lactylation modification proteins, which also plays critical role in However, it insufficient discuss glycolysis from single perspective. The intricate relationship between crucial promoting Thus, thorough elucidation underlying mediated by essential. This review provides comprehensive overview these further outlines exert synergistic effects, development creating positive feedback loop continues mediate this resistance. close link suggests application glycolysis-related drugs inhibitors cancer therapy may represent promising anticancer strategy. Furthermore, targeted lactylation, either alone combination with other treatments, offer new avenues overcoming
Language: Английский
Citations
0
Ageing Research Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 102670 - 102670
Published: Jan. 1, 2025
Language: Английский
Citations
0
Advanced Science, Journal Year: 2025, Volume and Issue: unknown
Published: March 27, 2025
Abstract Lactylation is a novel post‐translational modification mediated by lactate, widely present in the lysine residues of both histone and non‐histone proteins. However, specific regulatory mechanisms downstream target proteins remain unclear. Herein, it demonstrated that RCC2 protein may serve as critical link between material metabolism cell division, promoting rapid proliferation breast cancer under high glucose conditions. Mechanistically, activation glycolysis leads to an increase lactate. Then, acyltransferase KAT2A mediates lactylation at K124, which assists recruiting free SERBP1, thereby stabilizing MAD2L1 mRNA. The cellular signaling pathway contributes progression cancer. A small molecule inhibitor slows down binding active pocket specifically blocking lactylation. findings elucidate mechanism behind upregulation murine tumors associated with high‐sugar diet reported prior study suggest therapeutic strategy targeting restrict high‐lactate microenvironment.
Language: Английский
Citations
0
Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16
Published: May 12, 2025
Liver diseases pose a significant threat to human health. Lactate, byproduct of glycolysis, serves various biological functions, including acting as an energy source, signaling molecule, and substrate for lactylation. Lactylation is novel lactate-dependent post-translational modification that plays role in tumor proliferation, the regulation immune cell function, modulation gene expression. In this paper, we summarize roles lactate lactylation metabolism, inflammatory immunity, microenvironment, while also elucidating recent research advancements regarding context hepatic fibrosis, non-alcoholic fatty liver disease, hepatocellular carcinoma. Furthermore, are proposed promising new targets treatment diseases.
Language: Английский
Citations
0