Identification of lysine-lactylated substrates in gastric cancer cells

Yang, Dawei; Yin, Jie; Shan, Liuqun; Yi, Xingling; Zhang, Wei; Ding, Ye

doi:10.1016/j.isci.2022.104630

Cited by 40 publications

(63 citation statements)

References 32 publications

(42 reference statements)

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“…They used MS/MS analysis to identify 26 and 16 histone Kla sites from human MCF-7 cells and mouse bone marrow-derived macrophages (BMDM), respectively (9) (Figure 3A). Yang et al identified 27 histone Kla sites from gastric cancer AGS cells (8). Mouse cancer models show that the expression of the M2-like gene Arg1 is positively correlated with histone Kla levels.…”

Section: Lactylation Of Hcc Histone Lactylationmentioning

confidence: 99%

“…Normal cells produce large amounts of lactate only under hypoxic conditions, whereas tumor cells tend to convert pyruvate to lactate even when sufficient oxygen is present through the mitochondrial TCA cycle to support oxidative phosphorylation to generate ATP, the process is an aerobic glycolysis, also known as the "Warburg effect" (4,5). Lactylation is a novel post-translational modification (PTM) that includes histone lactylation and non-histone lactylation (6)(7)(8)(9). The large amount of lactate produced by tumor tissue through aerobic glycolysis provides a substrate for lactylation.…”

Section: Introductionmentioning

confidence: 99%

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Research progress of abnormal lactate metabolism and lactate modification in immunotherapy of hepatocellular carcinoma

Hao²,

Ren³

et al. 2023

Front. Oncol.

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Tumors meet their energy, biosynthesis, and redox demands through metabolic reprogramming. This metabolic abnormality results in elevated levels of metabolites, particularly lactate, in the tumor microenvironment. Immune cell reprogramming and cellular plasticity mediated by lactate and lactylation increase immunosuppression in the tumor microenvironment and are emerging as key factors in regulating tumor development, metastasis, and the effectiveness of immunotherapies such as immune checkpoint inhibitors. Reprogramming of glucose metabolism and the “Warburg effect” in hepatocellular carcinoma (HCC) lead to the massive production and accumulation of lactate, so lactate modification in tumor tissue is likely to be abnormal as well. This article reviews the immune regulation of abnormal lactate metabolism and lactate modification in hepatocellular carcinoma and the therapeutic strategy of targeting lactate-immunotherapy, which will help to better guide the medication and treatment of patients with hepatocellular carcinoma.

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Section: Lactylation Of Hcc Histone Lactylationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Research progress of abnormal lactate metabolism and lactate modification in immunotherapy of hepatocellular carcinoma

Hao²,

Ren³

et al. 2023

Front. Oncol.

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“… 232 With the help of other chemical tools such as alkynyl-functionalized bioorthogonal chemical reporter (YnLac), nonhistone Klac has also been reported by other studies in recent years. 233 , 234 The limited studies on nonhistone Klac have indicated its critical role in tumor, polymicrobial sepsis and retinopathy.…”

Section: Protein Acylation In Human Diseasesmentioning

confidence: 99%

Protein acylation: mechanisms, biological functions and therapeutic targets

Shang

Liu

Hua

2022

Sig Transduct Target Ther

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Metabolic reprogramming is involved in the pathogenesis of not only cancers but also neurodegenerative diseases, cardiovascular diseases, and infectious diseases. With the progress of metabonomics and proteomics, metabolites have been found to affect protein acylations through providing acyl groups or changing the activities of acyltransferases or deacylases. Reciprocally, protein acylation is involved in key cellular processes relevant to physiology and diseases, such as protein stability, protein subcellular localization, enzyme activity, transcriptional activity, protein–protein interactions and protein–DNA interactions. Herein, we summarize the functional diversity and mechanisms of eight kinds of nonhistone protein acylations in the physiological processes and progression of several diseases. We also highlight the recent progress in the development of inhibitors for acyltransferase, deacylase, and acylation reader proteins for their potential applications in drug discovery.

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“…In non-small cell lung cancer, lysine-lactylation sites were identified directly in the promoters of hexokinase-1 and isocitrate dehydrogenase, downregulating and upregulating their expression, respectively [ 132 ]. Additionally, in gastric cancer cells, more than 2000 sites for lysine-lactylation in non-histone proteins were identified, while lactylated lysines influenced RNA splicing and were more abundant in gastric tumors in comparison to adjacent tissue [ 133 ].…”

Section: Lactatementioning

confidence: 99%

Revisiting the Warburg Effect with Focus on Lactate

Kociánová

Piatrikova

Golias

2022

Cancers

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Rewired metabolism is acknowledged as one of the drivers of tumor growth. As a result, aerobic glycolysis, or the Warburg effect, is a feature of many cancers. Increased glucose uptake and glycolysis provide intermediates for anabolic reactions necessary for cancer cell proliferation while contributing sufficient energy. However, the accompanying increased lactate production, seemingly wasting glucose carbon, was originally explained only by the need to regenerate NAD+ for successive rounds of glycolysis by the lactate dehydrogenase (LDH) reaction in the cytosol. After the discovery of a mitochondrial LDH isoform, lactate oxidation entered the picture, and lactate was recognized as an important oxidative fuel. It has also been revealed that lactate serves a variety of signaling functions and helps cells adapt to the new environment. Here, we discuss recent findings on lactate metabolism and signaling in cancer while attempting to explain why the Warburg effect is adopted by cancer cells.

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Identification of lysine-lactylated substrates in gastric cancer cells

Cited by 40 publications

References 32 publications

Research progress of abnormal lactate metabolism and lactate modification in immunotherapy of hepatocellular carcinoma

Research progress of abnormal lactate metabolism and lactate modification in immunotherapy of hepatocellular carcinoma

Protein acylation: mechanisms, biological functions and therapeutic targets

Revisiting the Warburg Effect with Focus on Lactate

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