Metabolic reprogramming of glucose: the metabolic basis for the occurrence and development of hepatocellular carcinoma DOI Creative Commons
Kai Wang, Xiaodan Li,

Shuwei Guo

и другие.

Frontiers in Oncology, Год журнала: 2025, Номер 15

Опубликована: Фев. 6, 2025

Primary liver cancer is a common malignant tumor of the digestive system, with hepatocellular carcinoma (HCC) being most prevalent type. It characterized by high malignancy, insidious onset, and lack specific early diagnostic therapeutic markers, posing serious threat to human health. The occurrence development HCC are closely related its metabolic processes. Similar other tumors, reprogramming occurs extensively in cells, glucose metabolism particularly prominent. This abnormal activation glycolysis inhibition oxidative phosphorylation gluconeogenesis, among changes. Glucose provides intermediates energy for meet demands rapid growth, proliferation, metastasis. Additionally, various enzymes signaling molecules involved play irreplaceable roles. Therefore, regulating key pathways these processes considered an important target diagnosis treatment HCC. paper reviews current status progress HCC, aiming provide new insights diagnosis, detection, comprehensive strategies involving combined intervention clinical settings.

Язык: Английский

Phosphoenolpyruvate carboxykinase in cell metabolism: Roles and mechanisms beyond gluconeogenesis DOI Creative Commons
Shuo Yu,

Simin Meng,

Meixiang Xiang

и другие.

Molecular Metabolism, Год журнала: 2021, Номер 53, С. 101257 - 101257

Опубликована: Май 18, 2021

Phosphoenolpyruvate carboxykinase (PCK) has been almost exclusively recognized as a critical enzyme in gluconeogenesis, especially the liver and kidney. Accumulating evidence shown that enhanced activity of PCK leads to increased glucose output exacerbation diabetes, whereas defects result lethal hypoglycemia. Genetic mutations or polymorphisms are reported be related onset progression diabetes humans.

Язык: Английский

Процитировано

148
Targeting Pyrimidine Metabolism in the Era of Precision Cancer Medicine DOI Creative Commons
Wanyan Wang,

Jiayan Cui,

Hui Ma

и другие.

Frontiers in Oncology, Год журнала: 2021, Номер 11

Опубликована: Май 28, 2021

Metabolic rewiring is considered as a primary feature of cancer. Malignant cells reprogram metabolism pathway in response to various intrinsic and extrinsic drawback fuel cell survival growth. Among the complex metabolic pathways, pyrimidine biosynthesis conserved all living organism necessary maintain cellular fundamental function (i.e. DNA RNA biosynthesis). A wealth evidence has demonstrated that dysfunction closely related cancer progression numerous drugs targeting have been approved for multiple types However, non-negligible side effects limited efficacy warrants better strategy negating In recent years, increased studies evidenced interplay oncogenic signaling synthesis tumorigenesis. Here, we review conceptual advances on metabolism, especially dihydroorotate dehydrogenase (DHODH), framework precision oncology medicine prospect how this would guide development new drug precisely

Язык: Английский

Процитировано

115
Moonlighting functions of metabolic enzymes and metabolites in cancer DOI Creative Commons
Chaoyun Pan, Bo Li, M. Celeste Simon

и другие.

Molecular Cell, Год журнала: 2021, Номер 81(18), С. 3760 - 3774

Опубликована: Сен. 1, 2021

Язык: Английский

Процитировано

110
Deficiency of gluconeogenic enzyme PCK1 promotes metabolic-associated fatty liver disease through PI3K/AKT/PDGF axis activation in male mice DOI Creative Commons
Qian Ye, Yi Liu, Guiji Zhang

и другие.

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Март 14, 2023

Metabolic associated fatty liver disease (MAFLD) encompasses a broad spectrum of hepatic disorders, including steatosis, nonalcoholic steatohepatitis (NASH) and fibrosis. We demonstrated that phosphoenolpyruvate carboxykinase 1 (PCK1) plays central role in MAFLD progression. Male mice with Pck1 deficiency fed normal diet displayed lipid disorder injury, whereas fibrosis inflammation were aggravated high-fat drinking water containing fructose glucose (HFCD-HF/G). Forced expression PCK1 by adeno-associated virus ameliorated male mice. stimulated lipogenic gene synthesis. Moreover, loss activated the RhoA/PI3K/AKT pathway increasing intracellular GTP levels, secretion platelet-derived growth factor-AA (PDGF-AA), promoting stellate cell activation. Treatment RhoA AKT inhibitors or silencing AKT1 alleviated progression vivo. Hepatic may be important steatosis development through paracrine PDGF-AA mice, highlighting potential therapeutic strategy for MAFLD.

Язык: Английский

Процитировано

74
O-GlcNAcylation in cancer development and immunotherapy DOI

Xue-Fen He,

Xiaoli Hu,

Gao-Jing Wen

и другие.

Cancer Letters, Год журнала: 2023, Номер 566, С. 216258 - 216258

Опубликована: Июнь 4, 2023

Язык: Английский

Процитировано

42
Metabolic reprogramming in tumor immune microenvironment: Impact on immune cell function and therapeutic implications DOI Creative Commons
Yuqiang Liu,

Yu Zhao,

Huisheng Song

и другие.

Cancer Letters, Год журнала: 2024, Номер 597, С. 217076 - 217076

Опубликована: Июнь 19, 2024

Understanding of the metabolic reprogramming has revolutionized our insights into tumor progression and potential treatment. This review concentrates on aberrant pathways in cancer cells within microenvironment (TME). Cancer differ from normal their processing glucose, amino acids, lipids order to adapt heightened biosynthetic energy needs. These shifts, which crucially alter lactic acid, acid lipid metabolism, affect not only cell proliferation but also TME dynamics. explores various immune TME. From a therapeutic standpoint, targeting these alterations represents novel treatment strategy. discusses approaches regulation metabolism different nutrients influencing enhance response. In summary, this summarizes its as target for innovative strategies, offering fresh perspectives

Язык: Английский

Процитировано

18
Simultaneous 3-Nitrophenylhydrazine Derivatization Strategy of Carbonyl, Carboxyl and Phosphoryl Submetabolome for LC-MS/MS-Based Targeted Metabolomics with Improved Sensitivity and Coverage DOI

Xiangjun Meng,

Huanhuan Pang, Fei Sun

и другие.

Analytical Chemistry, Год журнала: 2021, Номер 93(29), С. 10075 - 10083

Опубликована: Июль 16, 2021

Metabolomics is a powerful and essential technology for profiling metabolic phenotypes exploring reprogramming, which enables the identification of biomarkers provides mechanistic insights into physiology disease. However, its applications are still limited by technical challenges particularly in detection sensitivity analysis biological samples with amount, necessitating development highly sensitive approaches. Here, we developed liquid chromatography tandem mass spectrometry method based on 3-nitrophenylhydrazine (3-NPH) derivatization strategy that simultaneously targets carbonyl, carboxyl, phosphoryl groups targeted metabolomic (HSDccp-TM) samples. By testing 130 endogenous metabolites including organic acids, amino carbohydrates, nucleotides, carnitines, vitamins, showed resulted significantly improved chromatographic separation capability. Metabolic merely 60 oocytes 5000 hematopoietic stem cells primarily isolated from mice demonstrated this enabled routine trace amounts biospecimens. Moreover, bypassed tediousness inferring MS fragmentation patterns simplified complexity monitoring ion pairs metabolites, greatly facilitated flux (MFA) glycolysis, tricarboxylic acid (TCA) cycle, pentose phosphate pathway (PPP) cell cultures. In summary, novel 3-NPH derivatization-based high sensitivity, good separation, broad coverage great potential promoting metabolomics MFA, especially

Язык: Английский

Процитировано

72
Emerging roles of cystathionine β-synthase in various forms of cancer DOI Creative Commons
Kelly Ascenção, Csaba Szabó

Redox Biology, Год журнала: 2022, Номер 53, С. 102331 - 102331

Опубликована: Май 10, 2022

The expression of the reverse transsulfuration enzyme cystathionine-β-synthase (CBS) is markedly increased in many forms cancer, including colorectal, ovarian, lung, breast and kidney, while other cancers (liver cancer glioma) it becomes downregulated. According to clinical database data high-CBS-expressor (e.g. colon or ovarian cancer), high CBS typically predicts lower survival, low-CBS-expressor liver low associated with survival. In high-CBS expressing tumor cells, CBS, its product hydrogen sulfide (H2S) serves as a bioenergetic, proliferative, cytoprotective stemness factor; also supports angiogenesis epithelial-to-mesenchymal transition microenvironment. current article reviews various tumor-cell-supporting roles CBS/H2S axis expressor overviews anticancer effects silencing pharmacological inhibition models vitro vivo; outlines potential approaches for biomarker identification, support future targeted therapies based on inhibition.

Язык: Английский

Процитировано

67
O-GlcNAcylation and stablization of SIRT7 promote pancreatic cancer progression by blocking the SIRT7-REGγ interaction DOI Creative Commons
Xiaoman He, Yongzhou Li, Qing Chen

и другие.

Cell Death and Differentiation, Год журнала: 2022, Номер 29(10), С. 1970 - 1981

Опубликована: Апрель 14, 2022

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers and its dismal prognosis indicates urgent need to elucidate potential oncogenic mechanisms. SIRT7 a classic NAD + -dependent deacetylase that stabilizes transformed state cancer cells. However, functional roles in PDAC are still unclear. Here, we found expression upregulated predicts poor PDAC. Then screened new interacting proteins by mass spectrometry results showed can interact with O-GlcNAc transferase (OGT). O-GlcNAcylation protein inhibiting interaction REGγ prevent degradation, hyper-O-GlcNAcylation pancreatic cells leads hypoacetylation H3K18 via SIRT7, which promotes transcriptional repression several tumour suppressor genes. In addition, at serine 136 residue (S136) required maintain stability deacetylation ability. vivo vitro experiments blocking S136 attenuates progression. Collectively, demonstrate an important post-translational modification cells, elucidating this mechanism expected pave way for development novel therapeutic methods future.

Язык: Английский

Процитировано

51
Gluconeogenic enzyme PCK1 supports S-adenosylmethionine biosynthesis and promotes H3K9me3 modification to suppress hepatocellular carcinoma progression DOI Creative Commons

Dongmei Gou,

Rui Liu,

Xiaoqun Shan

и другие.

Journal of Clinical Investigation, Год журнала: 2023, Номер 133(13)

Опубликована: Май 11, 2023

Deciphering the crosstalk between metabolic reprogramming and epigenetic regulation is a promising strategy for cancer therapy. In this study, we discovered that gluconeogenic enzyme PCK1 fueled generation of S-adenosylmethionine (SAM) through serine synthesis pathway. The methyltransferase SUV39H1 catalyzed SAM, which served as methyl donor to support H3K9me3 modification, leading suppression oncogene S100A11. Mechanistically, deficiency-induced oncogenic activation S100A11 was due its interaction with AKT1, upregulated PI3K/AKT signaling. Intriguingly, progression hepatocellular carcinoma (HCC) driven by deficiency suppressed SAM supplement or knockout in vivo vitro. These findings reveal availability key metabolite bridge connecting H3K9 trimethylation attenuating HCC progression, thus suggesting potential therapeutic against HCC.

Язык: Английский

Процитировано

30