Oncometabolites drive tumorigenesis by enhancing protein acylation: from chromosomal remodelling to nonhistone modification

Fu, Yidian; Yu, Jie; Li, Fang; Ge, Shengfang

doi:10.1186/s13046-022-02338-w

Cited by 39 publications

(26 citation statements)

References 210 publications

(249 reference statements)

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“…The great variability among lipids, in terms of their structure and properties, contributes to the remarkable diversity of lipid modifications. Among them, the most important is the acylation modification of proteins, in which FA is covalently linked to the peptide chain in the form of an acyl group 57 . In addition to classical lysine acetylation, many novel acylation modifications of histone and non-histone proteins, such as malonylation (Kma, mediated by malonyl-CoA), β-hydroxybutyrylation (Kbhb, mediated by β-hydroxybutyric acid; BHB), isoprene (mediated by intermediates of cholesterol synthesis), and long-chain fatty acid (LCFA) acylation, have been identified 58 .…”

Section: Specific Functions Of Lipids In Tumor Cellsmentioning

confidence: 99%

The role of lipid metabolic reprogramming in tumor microenvironment

Yang¹,

Wang²,

Song³

et al. 2023

Theranostics

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Metabolic reprogramming is one of the most important hallmarks of malignant tumors. Specifically, lipid metabolic reprogramming has marked impacts on cancer progression and therapeutic response by remodeling the tumor microenvironment (TME). In the past few decades, immunotherapy has revolutionized the treatment landscape for advanced cancers. Lipid metabolic reprogramming plays pivotal role in regulating the immune microenvironment and response to cancer immunotherapy. Here, we systematically reviewed the characteristics, mechanism, and role of lipid metabolic reprogramming in tumor and immune cells in the TME, appraised the effects of various cell death modes (specifically ferroptosis) on lipid metabolism, and summarized the antitumor therapies targeting lipid metabolism. Overall, lipid metabolic reprogramming has profound effects on cancer immunotherapy by regulating the immune microenvironment; therefore, targeting lipid metabolic reprogramming may lead to the development of innovative clinical applications including sensitizing immunotherapy.

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Section: Specific Functions Of Lipids In Tumor Cellsmentioning

confidence: 99%

The role of lipid metabolic reprogramming in tumor microenvironment

Yang¹,

Wang²,

Song³

et al. 2023

Theranostics

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“…PTM crosstalk is important for regulation of biological processes [60–62]. Here, we found that multiple PTMs occur on the same lysine of the same protein, for example 392 lysine sites were commonly modified by lactylation (Kla), crotonylation (Kcr), and 2-hydroxyisobutyrylation (Khib) (Figure S20, Table S26 and S27).…”

Section: Discussionmentioning

confidence: 93%

Protein Lactylation and Metabolic Regulation of the Zoonotic Parasite Toxoplasma gondii

Yin

Jiang

Cheng

et al. 2022

Preprint

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The biology of Toxoplasma gondii, the causative pathogen of one of the most wide-spread parasitic diseases remains poorly understood. Lactate, which is derived from glucose metabolic pathways, is considered to be not only an energy source in a variety of organisms including Toxoplasma gondii, but also a regulatory molecule that participates in gene activation and protein functioning. Lysine lactylation is a type of posttranslational modifications (PTMs) that was recently associated with chromatin remodeling, but lysine lactylation of histone and non-histone proteins has not yet been studied in T. gondii. To examine the prevalence and function of lactylation in T. gondii parasites, we mapped the lactylome of proliferating tachyzoite cells and found 1964 lactylation sites on 955 proteins in the T. gondii RH strain. The lactylated proteins were distributed in multiple subcellular compartments and were closely related to a wide variety of biological processes, including mRNA splicing, glycolysis, aminoacyl-tRNA biosynthesis, RNA transport, and multiple signaling pathways. We also performed chromatin immunoprecipitation sequencing (ChIP-seq) analysis with a lactylation specific antibody, the results revealed that histone H4K12la and H3K14la were enriched in the promoter and exon regions of Toxoplasma gondii genes associated with microtubule-based movement and cell invasion. We further confirmed the de-lactylase activity of histone deacetylase TgHDACs 2, 3, and 4, and that treatment with anti-histone acetyltransferase (TgMYST-A) antibodies profoundly reduced protein lactylation in the parasites. This study offers the first dataset of the global lactylation proteome and provides a basis for further dissection of the functional biology of Toxoplasma gondii.

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“…Free fatty acids not only fuel cancer progression through β-oxidation, but also serve as one of major metabolic resources generate abundant intermediate product within cells, such as lactate, Succ-CoA, Ac-CoA and BHB, which provide acyl-groups to covalently modify proteins, and then regulate their activity, subcellular localization or activated expression. These play dramatic roles in metabolomic-epigenetic and metabolomic-proteomic signaling in tumors(Fu et al, 2022; Sabari et al, 2017). On the other hand, it has been reported that low and high concentrations of FFA uptake by cancer cells could have either proliferative or lipotoxic effects, respectively, for example, arachidonic acid promotes proliferation at low concentrations but at high concentrations induces lipotoxicity through ferroptosis.…”

Section: Discussionmentioning

confidence: 99%

MIIP downregulation promotes colorectal cancer progression via inducing adjacent adipocytes browning

Wang

Ruiqi

et al. 2023

Preprint

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The enrichment of peri-cancerous adipocytes is one of the distinctive features of colorectal cancer (CRC), which accelerates the disease progression and worsens the prognosis. The communication between tumor cells and adjacent adipocytes plays an important role in this process. However, the detailed mechanisms remain largely unknown. Here we demonstrated MIIP is downregulated in high-grade CRC, and revealed its role and mechanism in tumor cell-adipocyte communication. By detecting MIIP expression in CRC tissues and adjacent normal tissues, we found MIIP was significantly decreased in CRC, and was closely related to adjacent adipocytes browning. In detail, MIIP reduction altered the N-linked glycosylation modification of AZGP1 and thus alleviated the inhibition of secretion. AZGP1, a critical lipid mobilization factor, led to the intensification of adipocytes browning and the release of free fatty acids (FFAs), which in turn fueled for CRC progression. Our data demonstrate that MIIP plays a key regulatory role in the communication between CRC and neighboring adipocytes by mediating AZGP1 secretion, and MIIP reduction leads to adipose browning-induced cancer rapid progression and poor prognosis.

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Oncometabolites drive tumorigenesis by enhancing protein acylation: from chromosomal remodelling to nonhistone modification

Cited by 39 publications

References 210 publications

The role of lipid metabolic reprogramming in tumor microenvironment

The role of lipid metabolic reprogramming in tumor microenvironment

Protein Lactylation and Metabolic Regulation of the Zoonotic Parasite Toxoplasma gondii

MIIP downregulation promotes colorectal cancer progression via inducing adjacent adipocytes browning

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