肿瘤代谢特点及其在肿瘤治疗中的应用进展
The Characteristics of Tumor Metabolism and Its Application Progress in Tumor Therapy
DOI: 10.12677/acm.2024.1461863, PDF,   
作者: 张城恺, 闫秋宇, 郝 爽, 曹栩嘉：空军军医大学基础医学院学员队，陕西 西安；王 文：空军军医大学唐都医院放射科，陕西 西安；刘正才*：空军军医大学西京医院综合外科，陕西 西安
关键词: 肿瘤代谢；肿瘤糖酵解；谷氨酰胺依赖；Tumor Metabolism； Tumor Glycolysis； Glutamine Dependence
摘要: 代谢重编程(metabolic reprogramming)是肿瘤的特征之一。本文针对肿瘤细胞中糖代谢、脂质代谢、氨基酸代谢、核苷酸代谢四种代谢类型进行综述。同时，我们阐述了特殊代谢产物在肿瘤中的变化及其调控机制，以更深入地认识肿瘤的代谢特点及其在肿瘤治疗中的研究进展。
Abstract: Metabolic reprogramming is one of the characteristics of tumors. In this paper, four metabolic types of glucose metabolism, lipid metabolism, amino acid metabolism and nucleotide metabolism in tumor cells were reviewed. At the same time, we discussed the changes of special metabolites in tumor and their regulatory mechanisms in order to further understand the characteristics of tumor metabolism and the research progress in tumor therapy.
文章引用：张城恺, 闫秋宇, 郝爽, 曹栩嘉, 王文, 刘正才. 肿瘤代谢特点及其在肿瘤治疗中的应用进展[J]. 临床医学进展, 2024, 14(6): 931-939. https://doi.org/10.12677/acm.2024.1461863

参考文献

[1] 龙常春, 唐思伟, 程忠平. 肿瘤细胞能量代谢的特点及调控机制[J]. 医学综述, 2017, 23(3): 479-483.
[2] 陆璐. 试论Warburg效应在肿瘤防治中的作用[J]. 东方药膳, 2021(6): 66.
[3] Li, Z. and Zhang, H. (2015) Reprogramming of Glucose, Fatty Acid and Amino Acid Metabolism for Cancer Progression. Cellular and Molecular Life Sciences, 73, 377-392. [Google Scholar] [CrossRef] [PubMed]
[4] 维帕威∙维萨瓦托尔, 贾萨达∙萨卡尔库, 卡莫尔波恩. 朗格洛杰金达, 等. 移植前AS-30D肝癌细胞状态决定其移植后在大白鼠体内的生长周期[J]. 实验动物科学, 2003, 20(z1): 34.
[5] Sebastian, S. and Kenkare, U.W. (1998) Expression of Two Type II-Like Tumor Hexokinase RNA Transcripts in Cancer Cell Lines. Tumor Biology, 19, 253-260. [Google Scholar] [CrossRef] [PubMed]
[6] Li, L., Li, L., Li, W., Chen, T., Zhao, L., et al. (2018) TAp73-Induced Phosphofructokinase-1 Transcription Promotes the Warburg Effect and Enhances Cell Proliferation. Nature Communications, 9, Article No. 4683. [Google Scholar] [CrossRef] [PubMed]
[7] Xie, H., Hanai, J., Ren, J., Kats, L., Burgess, K., Bhargava, P., et al. (2014) Targeting Lactate Dehydrogenase: A Inhibits Tumorigenesis and Tumor Progression in Mouse Models of Lung Cancer and Impacts Tumor-Initiating Cells. Cell Metabolism, 19, 795-809. [Google Scholar] [CrossRef] [PubMed]
[8] Shi, M., Cui, J., Du, J., Wei, D., Jia, Z., Zhang, J., et al. (2014) A Novel KLF4/LDHA Signaling Pathway Regulates Aerobic Glycolysis in and Progression of Pancreatic Cancer. Clinical Cancer Research, 20, 4370-4380. [Google Scholar] [CrossRef] [PubMed]
[9] Fantin, V.R., St-Pierre, J. and Leder, P. (2006) Attenuation of LDH-A Expression Uncovers a Link between Glycolysis, Mitochondrial Physiology, and Tumor Maintenance. Cancer Cell, 9, 425-434. [Google Scholar] [CrossRef] [PubMed]
[10] Cui, J., Shi, M., Xie, D., Wei, D., Jia, Z., Zheng, S., et al. (2014) FOXM1 Promotes the Warburg Effect and Pancreatic Cancer Progression via Transactivation of LDHA Expression. Clinical Cancer Research, 20, 2595-2606. [Google Scholar] [CrossRef] [PubMed]
[11] Jin, L., Chun, J., Pan, C., Alesi, G.N., Li, D., Magliocca, K.R., et al. (2017) Phosphorylation-Mediated Activation of LDHA Promotes Cancer Cell Invasion and Tumour Metastasis. Oncogene, 36, 3797-3806. [Google Scholar] [CrossRef] [PubMed]
[12] 阮丹. 肿瘤代谢研究进展综述[J]. 医学信息(下旬刊), 2013, 26(8): 688-689. [Google Scholar] [CrossRef] 
[13] Yao, P., Sun, H., Xu, C., Chen, T., Zou, B., Jiang, P., et al. (2017) Evidence for a Direct Cross-Talk between Malic Enzyme and the Pentose Phosphate Pathway via Structural Interactions. Journal of Biological Chemistry, 292, 17113-17120. [Google Scholar] [CrossRef] [PubMed]
[14] Nóbrega-Pereira, S., Fernandez-Marcos, P.J., Brioche, T., Gomez-Cabrera, M.C., Salvador-Pascual, A., Flores, J.M., et al. (2016) G6PD Protects from Oxidative Damage and Improves Healthspan in Mice. Nature Communications, 7, Article No. 10894. [Google Scholar] [CrossRef] [PubMed]
[15] Ananieva, E.A. and Wilkinson, A.C. (2018) Branched-Chain Amino Acid Metabolism in Cancer. Current Opinion in Clinical Nutrition & Metabolic Care, 21, 64-70. [Google Scholar] [CrossRef] [PubMed]
[16] Wang, Y.P., Zhou, L.S., Zhao, Y.Z., Wang, S.W., Chen, L.L., Liu, L.X., et al. (2014) Regulation of G6PD Acetylation by KAT9/SIRT2 Modulates NADPH Homeostasis and Cell Survival during Oxidative Stress. The EMBO Journal, 33, 1304-1320. [Google Scholar] [CrossRef] [PubMed]
[17] Sancak, Y., Peterson, T.R., Shaul, Y.D., Lindquist, R.A., Thoreen, C.C., Bar-Peled, L., et al. (2008) The Rag GTPases Bind Raptor and Mediate Amino Acid Signaling to mTORC1. Science, 320, 1496-1501. [Google Scholar] [CrossRef] [PubMed]
[18] Zhou, L., Wang, F., Sun, R., Chen, X., Zhang, M., Xu, Q., et al. (2016) SIRT5 Promotes IDH2 Desuccinylation and G6PD Deglutarylation to Enhance Cellular Antioxidant Defense. EMBO Reports, 17, 811-822. [Google Scholar] [CrossRef] [PubMed]
[19] Jiang, P., Du, W., Wang, X., Mancuso, A., Gao, X., Wu, M., et al. (2011) P53 Regulates Biosynthesis through Direct Inactivation of Glucose-6-Phosphate Dehydrogenase. Nature Cell Biology, 13, 310-316. [Google Scholar] [CrossRef] [PubMed]
[20] Donadio, A.C., Lobo, C., Tosina, M., de la Rosa, V., Martín‐Rufián, M., Campos‐Sandoval, J.A., et al. (2007) Antisense Glutaminase Inhibition Modifies the O‐GlcNAc Pattern and Flux through the Hexosamine Pathway in Breast Cancer Cells. Journal of Cellular Biochemistry, 103, 800-811. [Google Scholar] [CrossRef] [PubMed]
[21] Du, W., Jiang, P., Mancuso, A., Stonestrom, A., Brewer, M.D., Minn, A.J., et al. (2013) TAp73 Enhances the Pentose Phosphate Pathway and Supports Cell Proliferation. Nature Cell Biology, 15, 991-1000. [Google Scholar] [CrossRef] [PubMed]
[22] 徐梦婕, 黄耀, 谢国然, 等. E2F1与肿瘤代谢重编程的研究进展[J]. 实用医学杂志, 2014, 30(23): 3858-3860.
[23] 徐钰, 宋捷, 项蓉蓉, 等. 氨基酸代谢在抗肿瘤领域的研究进展[J]. 药物评价研究, 2018, 41(2): 340-344.
[24] Kinlaw, W.B., Baures, P.W., Lupien, L.E., Davis, W.L. and Kuemmerle, N.B. (2016) Fatty Acids and Breast Cancer: Make Them on Site or Have Them Delivered. Journal of Cellular Physiology, 231, 2128-2141. [Google Scholar] [CrossRef] [PubMed]
[25] Yi, M., Li, J., Chen, S., Cai, J., Ban, Y., Peng, Q., et al. (2018) Emerging Role of Lipid Metabolism Alterations in Cancer Stem Cells. Journal of Experimental & Clinical Cancer Research, 37, Article No. 118. [Google Scholar] [CrossRef] [PubMed]
[26] 王琼, 伍勇彬. RNA干扰ACLY表达对结肠癌SW480细胞周期、凋亡和AKT信号通路的影响[J]. 现代消化及介入诊疗, 2020, 25(1): 60-63.
[27] Hunkeler, M., Hagmann, A., Stuttfeld, E., Chami, M., Guri, Y., Stahlberg, H., et al. (2018) Structural Basis for Regulation of Human Acetyl-CoA Carboxylase. Nature, 558, 470-474. [Google Scholar] [CrossRef] [PubMed]
[28] 黄嘉琦, 秦晓东, 薛红宇, 秦泽莲. 脂肪酸代谢改变与肿瘤发生、发展的关系[J]. 医学综述, 2023, 29(7): 1318-1323.
[29] Xu, S., Chen, T., Dong, L., Li, T., Xue, H., Gao, B., et al. (2020) Fatty Acid Synthase Promotes Breast Cancer Metastasis by Mediating Changes in Fatty Acid Metabolism. Oncology Letters, 21, Article No. 27. [Google Scholar] [CrossRef] [PubMed]
[30] Jiang, W., Xing, X., Zhang, C., Yi, L., Xu, W., Ou, J., et al. (2021) MET and FASN as Prognostic Biomarkers of Triple Negative Breast Cancer: A Systematic Evidence Landscape of Clinical Study. Frontiers in Oncology, 11, Article ID: 604801. [Google Scholar] [CrossRef] [PubMed]
[31] Röhrig, F. and Schulze, A. (2016) The Multifaceted Roles of Fatty Acid Synthesis in Cancer. Nature Reviews Cancer, 16, 732-749. [Google Scholar] [CrossRef] [PubMed]
[32] 罗湘建, 曹亚. 肿瘤能量代谢机制研究进展[J]. 生物化学与生物物理进展, 2011, 38(7): 585-592. [Google Scholar] [CrossRef] 
[33] Santos, C.R. and Schulze, A. (2012) Lipid Metabolism in Cancer. The FEBS Journal, 279, 2610-2623. [Google Scholar] [CrossRef] [PubMed]
[34] Shamma, A., Takegami, Y., Miki, T., Kitajima, S., Noda, M., Obara, T., et al. (2009) Rb Regulates DNA Damage Response and Cellular Senescence through E2F-Dependent Suppression of N-Ras Isoprenylation. Cancer Cell, 15, 255-269. [Google Scholar] [CrossRef] [PubMed]
[35] Freed-Pastor, W.A., Mizuno, H., Zhao, X., Langerød, A., Moon, S., Rodriguez-Barrueco, R., et al. (2012) Mutant P53 Disrupts Mammary Tissue Architecture via the Mevalonate Pathway. Cell, 148, 244-258. [Google Scholar] [CrossRef] [PubMed]
[36] 王迪, 魏岚, 刘希, 等. 抗代谢类抗肿瘤药物对人肿瘤细胞中核苷酸代谢的影响[J]. 西北药学杂志, 2015(1): 59-65.
[37] Cory, J. and Sato, A. (1983) Regulation of Ribonucleotide Reductase Activity in Mammalian Cells. Molecular and Cellular Biochemistry, 53, 257-266. [Google Scholar] [CrossRef] [PubMed]
[38] 徐玲玲, 康丽峰, 刘高飞, 等. 嘌呤核苷磷酸化酶与嘧啶核苷磷酸化酶的融合表达及酶法合成嘌呤核苷类产物[J]. 生物加工过程, 2021, 19(1): 8-16.
[39] Lane, A.N. and Fan, T.W. (2015) Regulation of Mammalian Nucleotide Metabolism and Biosynthesis. Nucleic Acids Research, 43, 2466-2485. [Google Scholar] [CrossRef] [PubMed]
[40] 侯怡然, 李宝莉, 邢金良, 等. 肝癌代谢重编程研究及其临床应用进展[J]. 肿瘤代谢与营养电子杂志, 2019, 6(3): 295-300.
[41] Frederiks, W.M., Vizan, P., Bosch, K.S., Vreeling‐Sindelárová, H., Boren, J. and Cascante, M. (2008) Elevated Activity of the Oxidative and Non‐Oxidative Pentose Phosphate Pathway in (Pre)neoplastic Lesions in Rat Liver. International Journal of Experimental Pathology, 89, 232-240. [Google Scholar] [CrossRef] [PubMed]
[42] Howell, J.J., Ricoult, S.J.H., Ben-Sahra, I. and Manning, B.D. (2013) A Growing Role for mTOR in Promoting Anabolic Metabolism. Biochemical Society Transactions, 41, 906-912. [Google Scholar] [CrossRef] [PubMed]
[43] Ben-Sahra, I., Howell, J.J., Asara, J.M. and Manning, B.D. (2013) Stimulation of De Novo Pyrimidine Synthesis by Growth Signaling through mTOR and S6K1. Science, 339, 1323-1328. [Google Scholar] [CrossRef] [PubMed]
[44] Robitaille, A.M., Christen, S., Shimobayashi, M., Cornu, M., Fava, L.L., Moes, S., et al. (2013) Quantitative Phosphoproteomics Reveal mTORC1 Activates De Novo Pyrimidine Synthesis. Science, 339, 1320-1323. [Google Scholar] [CrossRef] [PubMed]
[45] Valvezan, A.J., Turner, M., Belaid, A., Lam, H.C., Miller, S.K., McNamara, M.C., et al. (2017) mTORC1 Couples Nucleotide Synthesis to Nucleotide Demand Resulting in a Targetable Metabolic Vulnerability. Cancer Cell, 32, 624-638.e5. [Google Scholar] [CrossRef] [PubMed]
[46] Ben-Sahra, I., Hoxhaj, G., Ricoult, S.J.H., Asara, J.M. and Manning, B.D. (2016) mTORC1 Induces Purine Synthesis through Control of the Mitochondrial Tetrahydrofolate Cycle. Science, 351, 728-733. [Google Scholar] [CrossRef] [PubMed]
[47] Pliszka, M. and Szablewski, L. (2021) Glucose Transporters as a Target for Anticancer Therapy. Cancers, 13, Article No. 4184. [Google Scholar] [CrossRef] [PubMed]
[48] Ozcan, S.C., Mutlu, A., Altunok, T.H., et al. (2021) Simultaneous Inhibition of PFKFB3 and GLS1 Selectively Kills KRAS-Transformed Pancreatic Cells. Biochemical and Biophysical Research Communications, 571, 118-124.
[49] 齐先梅, 罗娅, 王婧. 代谢重编程在肺动脉高压发病机制中的研究进展[J]. 中国病理生理杂志, 2021, 37(11): 2062-2071.
[50] Gnocchi, D., Sabbà, C., Massimi, M. and Mazzocca, A. (2023) Metabolism as a New Avenue for Hepatocellular Carcinoma Therapy. International Journal of Molecular Sciences, 24, Article No. 3710. [Google Scholar] [CrossRef] [PubMed]

为你推荐