每年出版 6 期
ISSN 打印: 1045-4403
ISSN 在线: 2162-6502
Indexed in
Carbon Source Metabolism and Its Regulation in Cancer Cells
摘要
Cancer cell proliferation and progression require sufficient supplies of nutrients including carbon sources, nitrogen sources, and molecular oxygen. Particularly, carbon sources and molecular oxygen are critical for the generation of ATP and building blocks, and for the maintenance of intracellular redox status. However, solid tumors frequently outgrow the blood supply, resulting in nutrient insufficiency. Accordingly, cancer cell metabolism shows aberrant biochemical features that are consequences of oncogenic signaling and adaptation. Those adaptive metabolism features, including the Warburg effect and addiction to glutamine, may form the biochemical basis for resistance to chemotherapy and radiation. A better understanding of the regulatory mechanisms that link the signaling pathways to adaptive metabolic reprogramming may identify novel biomarkers for drug development. In this review, we focus on the regulation of carbon source utilization at a cellular level, emphasizing its relevance to proliferative biosynthesis in cancer cells. We summarize the essential needs of proliferating cells and the metabolic features of glucose, lipids, and glutamine, and we review the roles of transcription regulators (i.e., HIF-1, c-Myc, and p53) and two major oncogenic signaling pathways (i.e., PI3K-Akt and MAPK) in regulating the utilization of carbon sources. Finally, the effects of glucose on cell proliferation and perspective from both biochemical and cellular angles are discussed.
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Li Weihua, Tai Yanhong, Zhou Jie, Gu Weiting, Bai Zhaofang, Zhou Tao, Zhong Zhijiu, McCue Peter A., Sang Nianli, Ji Jun-Yuan, Kong Beihua, Jiang Jie, Wang Chenguang, Repression of endometrial tumor growth by targeting SREBP1 and lipogenesis, Cell Cycle, 11, 12, 2012. Crossref
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Qie Shuo, Liang Dongming, Yin Chengqian, Gu Weiting, Meng Meng, Wang Chenguang, Sang Nianli, Glutamine depletion and glucose depletion trigger growth inhibition via distinctive gene expression reprogramming, Cell Cycle, 11, 19, 2012. Crossref
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Qie Shuo, Chu Clarissa, Li Weihua, Wang Chenguang, Sang Nianli, ErbB2 Activation Upregulates Glutaminase 1 Expression Which Promotes Breast Cancer Cell Proliferation, Journal of Cellular Biochemistry, 115, 3, 2014. Crossref
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Cetindis Marcel, Biegner Thorsten, Munz Adelheid, Teriete Peter, Reinert Siegmar, Grimm Martin, Glutaminolysis and carcinogenesis of oral squamous cell carcinoma, European Archives of Oto-Rhino-Laryngology, 273, 2, 2016. Crossref
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Li Zongwei, Wang Yingying, Newton Ian P., Zhang Lichao, Ji Pengyu, Li Zhuoyu, GRP78 is implicated in the modulation of tumor aerobic glycolysis by promoting autophagic degradation of IKKβ, Cellular Signalling, 27, 6, 2015. Crossref
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Elbaz Hosam A., Lee Icksoo, Antwih Deborah A., Liu Jenney, Hüttemann Maik, Zielske Steven P., Multhoff Gabriele, Epicatechin Stimulates Mitochondrial Activity and Selectively Sensitizes Cancer Cells to Radiation, PLoS ONE, 9, 2, 2014. Crossref
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Sun Yongyan, Shi Zhenhua, Lian Huiyong, Cai Peng, Energy metabolic dysfunction as a carcinogenic factor in cancer cells, Clinical and Translational Medicine, 5, 1, 2016. Crossref
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Hussain Saad A., Sulaiman Amal A., Balch Curt, Chauhan Harsh, Alhadidi Qasim M., Tiwari Amit K., Natural Polyphenols in Cancer Chemoresistance, Nutrition and Cancer, 68, 6, 2016. Crossref
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Eisenreich Wolfgang, Rudel Thomas, Heesemann Jürgen, Goebel Werner, To Eat and to Be Eaten: Mutual Metabolic Adaptations of Immune Cells and Intracellular Bacterial Pathogens upon Infection, Frontiers in Cellular and Infection Microbiology, 7, 2017. Crossref
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Sang Nianli, Yin Chengqian, Carbon Metabolism, in Encyclopedia of Cancer, 2014. Crossref
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Hsieh Feng-Shu, Hung Man-Hsin, Wang Cheng-Yi, Chen Yen-Lin, Hsiao Yung-Jen, Tsai Ming-Hsien, Li Jia-Rong, Chen Li-Ju, Shih Chih-Ting, Chao Tzu-I, Chen Kuen-Feng, Inhibition of protein phosphatase 5 suppresses non-small cell lung cancer through AMP-activated kinase activation, Lung Cancer, 112, 2017. Crossref
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Gillmaier Nadine, Götz Andreas, Schulz Anette, Eisenreich Wolfgang, Goebel Werner, Bruggemann Holger, Metabolic Responses of Primary and Transformed Cells to Intracellular Listeria monocytogenes, PLoS ONE, 7, 12, 2012. Crossref
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Mustafi Soumyajit Banerjee, Aznar Nicolas, Dhar Dwivedi Shailendra Kumar, Chakraborty Prabir Kumar, Basak Rumki, Mukherjee Priyabrata, Ghosh Pradipta, Bhattacharya Resham, Mitochondrial BMI1 maintains bioenergetic homeostasis in cells, The FASEB Journal, 30, 12, 2016. Crossref
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Conti Marc, Delvienne Thierry, Loric Sylvain, Combined Automated Measurement of Respiratory Chain Complexes and Oxidative Stress, in Mitochondrial Dysfunction Caused by Drugs and Environmental Toxicants, 2018. Crossref
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Qie Shuo, Diehl J. Alan, Glutamine addiction: an Achilles heel in esophageal cancers with dysregulation of CDK4/6, Molecular & Cellular Oncology, 6, 4, 2019. Crossref
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Eisenreich Wolfgang, Rudel Thomas, Heesemann Jürgen, Goebel Werner, How Viral and Intracellular Bacterial Pathogens Reprogram the Metabolism of Host Cells to Allow Their Intracellular Replication, Frontiers in Cellular and Infection Microbiology, 9, 2019. Crossref
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Sang Nianli, Yin Chengqian, Carbon Metabolism, in Encyclopedia of Cancer, 2014. Crossref
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Qie Shuo, Yoshida Akihiro, Parnham Stuart, Oleinik Natalia, Beeson Gyda C., Beeson Craig C., Ogretmen Besim, Bass Adam J., Wong Kwok-Kin, Rustgi Anil K., Diehl J. Alan, Targeting glutamine-addiction and overcoming CDK4/6 inhibitor resistance in human esophageal squamous cell carcinoma, Nature Communications, 10, 1, 2019. Crossref
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Qie Shuo, He Dan, Sang Nianli, Overview of Glutamine Dependency and Metabolic Rescue Protocols, in Cancer Metabolism, 1928, 2019. Crossref
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Pedroza-Torres Abraham, Romero-Córdoba Sandra L., Justo-Garrido Montserrat, Salido-Guadarrama Iván, Rodríguez-Bautista Rubén, Montaño Sarita, Muñiz-Mendoza Rodolfo, Arriaga-Canon Cristian, Fragoso-Ontiveros Verónica, Álvarez-Gómez Rosa María, Hernández Greco, Herrera Luis A., MicroRNAs in Tumor Cell Metabolism: Roles and Therapeutic Opportunities, Frontiers in Oncology, 9, 2019. Crossref
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Han Changpeng, Yang Haojie, Li Bin, Wang Zhenyi, Exogenous pyruvate facilitates ultraviolet B-induced DNA damage repair by promoting H3K9 acetylation in keratinocytes and melanocytes, Biomedicine & Pharmacotherapy, 126, 2020. Crossref
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Qie Shuo, Diehl J. Alan, Cyclin D degradation by E3 ligases in cancer progression and treatment, Seminars in Cancer Biology, 67, 2020. Crossref
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Li Weihua, Bai Huimin, Liu Shiping, Cao Dongyan, Wu Hongying, Shen Keng, Tai Yanhong, Yang Jiaxin, Targeting stearoyl-CoA desaturase 1 to repress endometrial cancer progression, Oncotarget, 9, 15, 2018. Crossref
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Eisenreich Wolfgang, Heesemann Jürgen, Rudel Thomas, Goebel Werner, Metabolic Adaptations of Intracellullar Bacterial Pathogens and their Mammalian Host Cells during Infection (“Pathometabolism”), in Metabolism and Bacterial Pathogenesis, 2015. Crossref
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Yin Chengqian, He Dan, Chen Shuyang, Tan Xiaoling, Sang Nianli, Exogenous pyruvate facilitates cancer cell adaptation to hypoxia by serving as an oxygen surrogate, Oncotarget, 7, 30, 2016. Crossref
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Li Zongwei, Wang Yingying, Wu Haili, Zhang Lichao, Yang Peng, Li Zhuoyu, GRP78 enhances the glutamine metabolism to support cell survival from glucose deficiency by modulating the β-catenin signaling, Oncotarget, 5, 14, 2014. Crossref
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O'Neill Edward N., Cosenza Zachary A., Baar Keith, Block David E., Considerations for the development of cost‐effective cell culture media for cultivated meat production, Comprehensive Reviews in Food Science and Food Safety, 20, 1, 2021. Crossref
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Hu Tu, He Nengbin, Yang Yunsong, Yin Chengqian, Sang Nianli, Yang Qingcheng, DEC2 expression is positively correlated with HIF-1 activation and the invasiveness of human osteosarcomas, Journal of Experimental & Clinical Cancer Research, 34, 1, 2015. Crossref
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Millet-Boureima Cassandra, He Stephanie, Le Thi Bich Uyen, Gamberi Chiara, Modeling Neoplastic Growth in Renal Cell Carcinoma and Polycystic Kidney Disease, International Journal of Molecular Sciences, 22, 8, 2021. Crossref
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Lin Shaojun, Guo Qiaojuan, Wen Jiangmei, Li Chao, Lin Jin, Cui Xiaofei, Sang Nianli, Pan Jianji, Survival analyses correlate stanniocalcin 2 overexpression to poor prognosis of nasopharyngeal carcinomas, Journal of Experimental & Clinical Cancer Research, 33, 1, 2014. Crossref
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Khan Asifa, Siddiqui Shumaila, Husain Syed Akhtar, Mazurek Sybille, Iqbal Mohammad Askandar, Phytocompounds Targeting Metabolic Reprogramming in Cancer: An Assessment of Role, Mechanisms, Pathways, and Therapeutic Relevance, Journal of Agricultural and Food Chemistry, 69, 25, 2021. Crossref
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Gibart Laetitia, Khoodeeram Rajeev, Bernot Gilles, Comet Jean-Paul, Trosset Jean-Yves, Regulation of Eukaryote Metabolism: An Abstract Model Explaining the Warburg/Crabtree Effect, Processes, 9, 9, 2021. Crossref
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Madsen Sanne Kjærulf, Priess Camilla, Wätjen Anders Peter, Øzmerih Süleyman, Mohammadifar Mohammad Amin, Heiner Bang-Berthelsen Claus, Development of a yoghurt alternative, based on plant-adapted lactic acid bacteria, soy drink and the liquid fraction of brewers’ spent grain, FEMS Microbiology Letters, 368, 15, 2021. Crossref
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Traversa Debora, Simonetti Giorgia, Tolomeo Doron, Visci Grazia, Macchia Gemma, Ghetti Martina, Martinelli Giovanni, Kristensen Lasse S., Storlazzi Clelia Tiziana, Unravelling similarities and differences in the role of circular and linear PVT1 in cancer and human disease, British Journal of Cancer, 126, 6, 2022. Crossref
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Loric Sylvain, Conti Marc, Versatile Functional Energy Metabolism Platform Working From Research to Patient: An Integrated View of Cell Bioenergetics, Frontiers in Toxicology, 3, 2022. Crossref
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Radlinski Lauren C., Brunton Jason, Steele Shaun, Taft-Benz Sharon, Kawula Thomas H., Shuman Howard A., Defining the Metabolic Pathways and Host-Derived Carbon Substrates Required for Francisella tularensis Intracellular Growth, mBio, 9, 6, 2018. Crossref
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Eisenreich Wolfgang, Heesemann Jürgen, Rudel Thomas, Goebel Werner, Conway Tyrrell, Cohen Paul, Metabolic Adaptations of Intracellullar Bacterial Pathogens and their Mammalian Host Cells during Infection (“Pathometabolism”), Microbiology Spectrum, 3, 3, 2015. Crossref
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Qie Shuo, Sang Nianli, Stanniocalcin 2 (STC2): a universal tumour biomarker and a potential therapeutical target, Journal of Experimental & Clinical Cancer Research, 41, 1, 2022. Crossref
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Gallegos-Martínez Salvador, Lara-Mayorga Itzel Montserrat, Samandari Mohamadmahdi, Mendoza-Buenrostro Christian, Flores-Garza Brenda Giselle, Reyes-Cortés Luisa María, Segoviano-Ramírez Juan Carlos, Zhang Yu Shrike, Trujillo-de Santiago Grissel, Álvarez Mario Moisés, Culture of cancer spheroids and evaluation of anti-cancer drugs in 3D-printed miniaturized continuous stirred tank reactors (mCSTRs), Biofabrication, 14, 3, 2022. Crossref
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Kim Seon Yoo, Kim Dongwoo, Kim Jisu, Ko Hae Young, Kim Won Jin, Park Youngjoo, Lee Hye Won, Han Dai Hoon, Kim Kyung Sik, Park Sunghyouk, Lee Misu, Yun Mijin, Extracellular Citrate Treatment Induces HIF1α Degradation and Inhibits the Growth of Low-Glycolytic Hepatocellular Carcinoma under Hypoxia, Cancers, 14, 14, 2022. Crossref