The function and mechanism of lactate and lactylation in tumor metabolism and microenvironment DOI Creative Commons
Yan Zhang, Qiu Peng, Jinhua Zheng

et al.

Genes & Diseases, Journal Year: 2022, Volume and Issue: 10(5), P. 2029 - 2037

Published: Oct. 19, 2022

Lactate is an end product of glycolysis. Owing to the lactate shuttle concept introduced in early 1980s, increasing researchers indicate as a critical energy source for mitochondrial respiration and precursor gluconeogenesis. also acts multifunctional signaling molecule through receptors expressed various cells, resulting diverse biological consequences including decreased lipolysis, immune regulation, anti-inflammation wound healing, enhanced exercise performance association with gut microbiome. Furthermore, evidence reveals that contributes epigenetic gene regulation by lactylating lysine residues histones, which accounts its key role modulation maintenance homeostasis. Here, we summarize function mechanism lactylation tumor metabolism microenvironment.

Language: Английский

Crosstalk between glucose metabolism, lactate production and immune response modulation DOI
Lei Ye, Yi Jiang, Mingming Zhang

et al.

Cytokine & Growth Factor Reviews, Journal Year: 2022, Volume and Issue: 68, P. 81 - 92

Published: Nov. 7, 2022

Language: Английский

Citations

147
Tumor-derived lactate promotes resistance to bevacizumab treatment by facilitating autophagy enhancer protein RUBCNL expression through histone H3 lysine 18 lactylation (H3K18la) in colorectal cancer DOI Creative Commons
Weihao Li, Chi Zhou, Long Yu

et al.

Autophagy, Journal Year: 2023, Volume and Issue: 20(1), P. 114 - 130

Published: Aug. 24, 2023

Bevacizumab plays an important role in the first and second line treatment for metastatic colorectal cancer (CRC). And induction of hypoxia tumors response to it determining efficacy antiangiogenic therapy while connection between them remains unclear. Here, we found that lactate accumulated tumor environment CRC acted as substrates histone lactylation, this process was further induced by cellular enhanced glycolysis hypoxia. We determined patients resistant bevacizumab presented with elevated levels lactylation inhibition efficiently suppressed tumorigenesis, progression survival Histone promoted transcription RUBCNL/Pacer, facilitating autophagosome maturation through interacting BECN1 (beclin 1) mediating recruitment function class III phosphatidylinositol 3-kinase complex, which had a crucial hypoxic cells proliferation survival. Moreover, combining macroautophagy/autophagy demonstrated remarkable bevacizumab-resistance patients-derived pre-clinical models. These findings delivered new exploration supplement metabolic reprogramming-epigenetic regulation, provided strategy improving clinical lactylation.

Language: Английский

Citations

121
Targeting protein modifications in metabolic diseases: molecular mechanisms and targeted therapies DOI Creative Commons
Xiumei Wu, Mengyun Xu,

M. Geng

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 27, 2023

The ever-increasing prevalence of noncommunicable diseases (NCDs) represents a major public health burden worldwide. most common form NCD is metabolic diseases, which affect people all ages and usually manifest their pathobiology through life-threatening cardiovascular complications. A comprehensive understanding the will generate novel targets for improved therapies across spectrum. Protein posttranslational modification (PTM) an important term that refers to biochemical specific amino acid residues in target proteins, immensely increases functional diversity proteome. range PTMs includes phosphorylation, acetylation, methylation, ubiquitination, SUMOylation, neddylation, glycosylation, palmitoylation, myristoylation, prenylation, cholesterylation, glutathionylation, S-nitrosylation, sulfhydration, citrullination, ADP ribosylation, several PTMs. Here, we offer review roles pathological consequences, including diabetes, obesity, fatty liver hyperlipidemia, atherosclerosis. Building upon this framework, afford description proteins pathways involved by focusing on PTM-based protein modifications, showcase pharmaceutical intervention preclinical studies clinical trials, future perspectives. Fundamental research defining mechanisms whereby regulate open new avenues therapeutic intervention.

Language: Английский

Citations

99
SIRT3‐dependent delactylation of cyclin E2 prevents hepatocellular carcinoma growth DOI Creative Commons

Jing Jin,

Lin Bai, Dongyao Wang

et al.

EMBO Reports, Journal Year: 2023, Volume and Issue: 24(5)

Published: March 10, 2023

Language: Английский

Citations

93
An Epigenetic Role of Mitochondria in Cancer DOI Creative Commons
Yue Liu, Chao Chen, Xinye Wang

et al.

Cells, Journal Year: 2022, Volume and Issue: 11(16), P. 2518 - 2518

Published: Aug. 13, 2022

Mitochondria are not only the main energy supplier but also cell metabolic center regulating multiple key metaborates that play pivotal roles in epigenetics regulation. These metabolites include acetyl-CoA, α-ketoglutarate (α-KG), S-adenosyl methionine (SAM), NAD+, and O-linked beta-N-acetylglucosamine (O-GlcNAc), which substrates for DNA methylation histone post-translation modifications, essential gene transcriptional regulation fate determination. Tumorigenesis is attributed to many factors, including mutations tumor microenvironment. initiation, evolution, metastasis, recurrence. Targeting mitochondrial metabolism promising therapeutic strategies treatment. In this review, we summarize of mitochondria required modification discuss current strategy cancer therapies via targeting epigenetic modifiers related enzymes This review an important contribution understanding metabolic-epigenetic-tumorigenesis concept.

Language: Английский

Citations

87
Lactate, histone lactylation and cancer hallmarks DOI

Xinyu Lv,

Yingying Lv, Xiaofeng Dai

et al.

Expert Reviews in Molecular Medicine, Journal Year: 2023, Volume and Issue: 25

Published: Jan. 1, 2023

Abstract Histone lactylation, an indicator of lactate level and glycolysis, has intrinsic connections with cell metabolism that represents a novel epigenetic code affecting the fate cells including carcinogenesis. Through delineating relationship between histone lactylation cancer hallmarks, we propose as priming toward malignant state, advocate importance identifying therapeutic strategies or dual-targeting modalities against effective control. This review underpins important yet less-studied area in sheds insights on its clinical impact well possible tools targeting lactylation.

Language: Английский

Citations

80
Lactate‐induced protein lactylation: A bridge between epigenetics and metabolic reprogramming in cancer DOI Creative Commons
Ting Wang, Ye Zeng, Zheng Li

et al.

Cell Proliferation, Journal Year: 2023, Volume and Issue: 56(10)

Published: April 14, 2023

Lactate is not only an endpoint of glycolysis but gradually being discovered to play the role a universal metabolic fuel for energy via 'lactate shuttle' moving between cells and transmitting signals. The glycolytic-dependent metabolism found in tumours fast-growing has made lactate pivotal player reprogramming, which enables obtain abundant short time. Moreover, can provide favourable conditions tumorigenesis by shaping acidic tumour microenvironment, recruiting immune cells, etc. recently lactate-induced lactylation moves even further on pro-tumorigenesis mechanisms production, circulation utilization. As with other epigenetic modifications, modify histone proteins alter spatial configuration chromatin, affect DNA accessibility regulate expression corresponding genes. What's more, degree inseparable from spatialized concentration, builds bridge epigenetics reprogramming. Here, we review important summarize latest finding try explore therapeutic strategies oncotherapy that kill two birds one stone.

Language: Английский

Citations

78
AMPK and NRF2: Interactive players in the same team for cellular homeostasis? DOI Creative Commons

Eleni Petsouki,

Shara Natalia Sosa Cabrera,

Elke H. Heiß

et al.

Free Radical Biology and Medicine, Journal Year: 2022, Volume and Issue: 190, P. 75 - 93

Published: July 31, 2022

NRF2 (Nuclear factor E2 p45‐related 2) is a stress responsive transcription lending cells resilience against oxidative, xenobiotic, and also nutrient or proteotoxic insults. AMPK (AMP-activated kinase), considered as prime regulator of cellular energy homeostasis, not only tunes metabolism to provide the cell at any time with sufficient ATP building blocks, but controls redox balance inflammation. Due observed overlapping responses upon activation common stressors impinging on both signaling, it plausible assume that signaling may interdepend cooperate readjust homeostasis. After short introduction two players this narrative review paints current picture how might interact molecular level, highlights their possible crosstalk in selected examples pathophysiology bioactivity drugs phytochemicals.

Language: Английский

Citations

74
H3K18 lactylation promotes the progression of arsenite-related idiopathic pulmonary fibrosis via YTHDF1/m6A/NREP DOI

Peiwen Wang,

Daxiao Xie,

Tian Xiao

et al.

Journal of Hazardous Materials, Journal Year: 2023, Volume and Issue: 461, P. 132582 - 132582

Published: Sept. 19, 2023

Language: Английский

Citations

57
Epigenetic mechanisms of Immune remodeling in sepsis: targeting histone modification DOI Creative Commons
Dan Wu,

Yuxin Shi,

Hao Zhang

et al.

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(2)

Published: Feb. 11, 2023

Abstract Sepsis is a life-threatening disorder disease defined as infection-induced dysregulated immune responses and multiple organ dysfunction. The imbalance between hyperinflammation immunosuppression crucial feature of sepsis immunity. Epigenetic modifications, including histone DNA methylation, chromatin remodeling, non-coding RNA, play essential roles in regulating immunity through epi-information independent the sequence. In recent years, mechanisms modification have received increasing attention, with ongoing discoveries novel types modifications. Due to capacity for prolonged effects on cells, modifications can induce cell reprogramming participate long-term immunosuppressed state sepsis. Herein, we systematically review current involved regulation sepsis, summarize their role from an perspective provide potential therapeutic opportunities targeting treatment.

Language: Английский

Citations

53