Lactate and lactylation in gastrointestinal cancer: Current progress and perspectives (Review) DOI Creative Commons

Yufen He,

Yanbin Huang, Peng Peng

и другие.

Oncology Reports, Год журнала: 2024, Номер 53(1)

Опубликована: Ноя. 8, 2024

Gastrointestinal (GI) cancers, which have notable incidence and mortality, are impacted by metabolic reprogramming, especially the increased production accumulation of lactate. Lactylation, a post‑translational modification driven lactate, is crucial regulator gene expression cellular function in GI cancer. The present review aimed to examine advancements understanding lactate lactylation mechanisms production, its influence on tumor microenvironment clinical implications levels as potential biomarkers were explored. Furthermore, was investigated, including biochemical foundation, primary targets functional outcomes. underscored therapeutic strategies targeting metabolism lactylation. Challenges future directions emphasize innovative cancer improve

Язык: Английский

Anaerobic metabolism promotes breast cancer survival via Histone-3 Lysine-18 lactylation mediating PPARD axis DOI Creative Commons
Ying Xu,

Weiwei Meng,

Yingqi Dai

и другие.

Cell Death Discovery, Год журнала: 2025, Номер 11(1)

Опубликована: Фев. 8, 2025

Abstract Histone lactylation plays a crucial role in cancer progression, but its impact on breast (BC) tumorigenesis is still unclear. We utilized chromatin immunoprecipitation sequencing with H3K18la antibodies, transcriptomics of clinical BC samples, and proteomics ATAC-seq analyses vivo tumors to identify the genes regulated by transcription factor PPARD. qPCR Western blot assays were used detect expressions molecules. discovered that levels higher tissues compared adjacent non-cancerous tissues. promoted expression PPARD, which turn influenced AKT, not ILK. analysis revealed glycolysis cells enhanced accessibility. Additionally, we confirmed HDAC2 HDAC3 act as “erasers” for H3 lysine lactylation. During analysis, AKT-phosphorylation aerobic respiration inhibitor group exhibited an apparent disparity activity. Our study demonstrated changes downstream PPARD support cell survival under anaerobic conditions. accelerated proliferation promoting phosphorylation AKT. This highlights therapeutic potential targeting H3K18la/PPARD/AKT axis cancer, providing new insights into epigenetic regulation metabolism (Trial registration: The was approved Research Ethics Committee Shandong Provincial Third Hospital (KYLL-2023057; https://www.medicalresearch.org.cn/ )).

Язык: Английский

Процитировано

2
Lactate-induced protein lactylation in cancer: functions, biomarkers and immunotherapy strategies DOI Creative Commons
Wenjuan Wang, Hong Wang, Qi Wang

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 15

Опубликована: Янв. 10, 2025

Lactate, long viewed as a byproduct of glycolysis and metabolic waste. Initially identified within the context yogurt fermentation, lactate's role extends beyond culinary applications to its significance in biochemical processes. Contemporary research reveals that lactate functions not merely terminal product but also nexus for initiating physiological pathological responses body. Lysine lactylation (Kla), novel post-translational modification (PTM) proteins, has emerged pivotal mechanism by which exerts regulatory influence. This epigenetic potential alter gene expression patterns, thereby impacting Increasing evidence indicates correlation between adverse prognosis various malignancies. Consequently, this review article aims encapsulate proteins interact with lactate, elucidate tumorigenesis progression, explore therapeutic targets afforded modulation lactylation. The objective is clarify oncogenic provide strategic framework future directions burgeoning field.

Язык: Английский

Процитировано

1
Lactylation in cancer: Mechanisms in tumour biology and therapeutic potentials DOI Creative Commons
Yipeng He,

Tianbao Song,

Jinzhuo Ning

и другие.

Clinical and Translational Medicine, Год журнала: 2024, Номер 14(11)

Опубликована: Окт. 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.

Язык: Английский

Процитировано

6
Lactylation in health and disease: physiological or pathological? DOI Creative Commons
Lijun Zhao,

Haonan Qi,

Huiying Lv

и другие.

Theranostics, Год журнала: 2025, Номер 15(5), С. 1787 - 1821

Опубликована: Янв. 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.

Язык: Английский

Процитировано

0
Diagnostic value of a lactylation-related gene signature in hepatocellular carcinoma DOI Open Access

Jiajia Zhang,

Chunmei Dong,

Lili Wu

и другие.

Translational Cancer Research, Год журнала: 2025, Номер 14(1), С. 296 - 312

Опубликована: Янв. 1, 2025

The occurrence rate of liver cancer is increasing in recent years. significance lactylation tumor cells should not be neglected. This study aimed to discover a gene signature related that can used for diagnostic applications. Data were downloaded from Cancer Genome Atlas (TCGA), GSE14520, GSE84402, and GSE62232 datasets. Differential analysis random forest performed hepatocellular carcinoma (HCC). Receiver operating characteristic (ROC) curve was evaluate efficiency, logistic regression established obtain the risk score equation. Besides, expression genes identified by TCGA database verified real-time quantitative polymerase chain reaction (RT-PCR). In order analyze prognostic performance, patients diagnosed with HCC stratified into either high or low categories based on median score. addition, immunotherapy drug sensitivity groups assessed. performance model validated Gene Expression Omnibus (GEO) dataset. had worse outcomes than those database. ROC curves showed characteristics lactylation-related good predictive capability. Furthermore, we developed nomogram patients, utilizing data resources TCGA. Finally, terms assessing potency group lower Tumor Immune Dysfunction Exclusion (TIDE) score, indicating response immunotherapy. Our identification associated presents promising avenue development targeted immunotherapeutic strategies.

Язык: Английский

Процитировано

0
Lactylation modification in cancer: mechanisms, functions, and therapeutic strategies DOI Creative Commons
Mengqi Lv,

Yefei Huang,

Yansu Chen

и другие.

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

Процитировано

0
The lactylation modification of proteins plays a critical role in tumor progression DOI Creative Commons

Dai Yi,

Ke Zhou,

Yu Pan

и другие.

Frontiers in Oncology, Год журнала: 2025, Номер 15

Опубликована: Март 19, 2025

Lactylation modifications have been shown to be a novel type of protein post-translational (PTMs), providing new perspective for understanding the interaction between cellular metabolic reprogramming and epigenetic regulation. Studies that lactylation plays an important role in occurrence, development, angiogenesis, invasion metastasis tumors. It can not only regulate phenotypic expression functional polarization immune cells, but also participate formation tumor drug resistance through variety molecular mechanisms. In this review, we review latest research progress modification tumors, focusing on its mechanism action cell regulation microenvironment (TME), resistance, aiming provide theoretical basis ideas discovery therapeutic targets methods. Through in-depth analysis modification, it is expected open up direction treatment potential strategies overcoming improving clinical efficacy.

Язык: Английский

Процитировано

0
H3K9/18 lactylation regulates DNA damage due to nickel exposure in human bronchial epithelial cells DOI

Xiaomin Xie,

Chaowei Wen, Quekun Peng

и другие.

Toxicology and Applied Pharmacology, Год журнала: 2025, Номер 499, С. 117347 - 117347

Опубликована: Апрель 16, 2025

Язык: Английский

Процитировано

0
Lactylation in cancer progression and drug resistance DOI
Yuxiu Sun, He Wang,

Zhe Cui

и другие.

Drug Resistance Updates, Год журнала: 2025, Номер unknown, С. 101248 - 101248

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

0
Lactate and lactylation in gastrointestinal cancer: Current progress and perspectives (Review) DOI Creative Commons

Yufen He,

Yanbin Huang, Peng Peng

и другие.

Oncology Reports, Год журнала: 2024, Номер 53(1)

Опубликована: Ноя. 8, 2024

Gastrointestinal (GI) cancers, which have notable incidence and mortality, are impacted by metabolic reprogramming, especially the increased production accumulation of lactate. Lactylation, a post‑translational modification driven lactate, is crucial regulator gene expression cellular function in GI cancer. The present review aimed to examine advancements understanding lactate lactylation mechanisms production, its influence on tumor microenvironment clinical implications levels as potential biomarkers were explored. Furthermore, was investigated, including biochemical foundation, primary targets functional outcomes. underscored therapeutic strategies targeting metabolism lactylation. Challenges future directions emphasize innovative cancer improve

Язык: Английский

Процитировано

0