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      The role of ubiquitination and deubiquitination in cancer metabolism

      review-article
      1 , 2 , 1 ,
      Molecular Cancer
      BioMed Central
      Ubiquitination, Deubiquitination, Cancer, Metabolic reprogramming

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          Abstract

          Metabolic reprogramming, including enhanced biosynthesis of macromolecules, altered energy metabolism, and maintenance of redox homeostasis, is considered a hallmark of cancer, sustaining cancer cell growth. Multiple signaling pathways, transcription factors and metabolic enzymes participate in the modulation of cancer metabolism and thus, metabolic reprogramming is a highly complex process. Recent studies have observed that ubiquitination and deubiquitination are involved in the regulation of metabolic reprogramming in cancer cells. As one of the most important type of post-translational modifications, ubiquitination is a multistep enzymatic process, involved in diverse cellular biological activities. Dysregulation of ubiquitination and deubiquitination contributes to various disease, including cancer. Here, we discuss the role of ubiquitination and deubiquitination in the regulation of cancer metabolism, which is aimed at highlighting the importance of this post-translational modification in metabolic reprogramming and supporting the development of new therapeutic approaches for cancer treatment.

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          Most cited references187

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          Lactate Metabolism in Human Lung Tumors

          Cancer cells consume glucose and secrete lactate in culture. It is unknown whether lactate contributes to energy metabolism in living tumors. We previously reported that human non-small cell lung cancers (NSCLC) oxidize glucose in the tricarboxylic acid (TCA) cycle. Here we show that lactate is also a TCA cycle carbon source for NSCLC. In human NSCLC, evidence of lactate utilization was most apparent in tumors with high 18 fluorodeoxyglucose uptake and aggressive oncological behavior. Infusing human NSCLC patients with 13 C-lactate revealed extensive labeling of TCA cycle metabolites. In mice, deleting monocarboxylate transporter-1 (MCT1) from tumor cells eliminated lactate-dependent metabolite labeling, confirming tumor-cell autonomous lactate uptake. Strikingly, directly comparing lactate and glucose metabolism in vivo indicated that lactate's contribution to the TCA cycle predominates. The data indicate that tumors, including bona fide human NSCLC, can use lactate as a fuel in vivo. Human non-small cell lung cancer preferentially utilizes lactate over glucose to fuel TCA cycle and sustain tumor metabolism in vivo.
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            Ubiquitination in disease pathogenesis and treatment.

            Ubiquitination is crucial for a plethora of physiological processes, including cell survival and differentiation and innate and adaptive immunity. In recent years, considerable progress has been made in the understanding of the molecular action of ubiquitin in signaling pathways and how alterations in the ubiquitin system lead to the development of distinct human diseases. Here we describe the role of ubiquitination in the onset and progression of cancer, metabolic syndromes, neurodegenerative diseases, autoimmunity, inflammatory disorders, infection and muscle dystrophies. Moreover, we indicate how current knowledge could be exploited for the development of new clinical therapies.
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              Reprogramming of glucose, fatty acid and amino acid metabolism for cancer progression.

              Metabolic reprogramming is widely observed during cancer development to confer cancer cells the ability to survive and proliferate, even under the stressed, such as nutrient-limiting, conditions. It is famously known that cancer cells favor the "Warburg effect", i.e., the enhanced glycolysis or aerobic glycolysis, even when the ambient oxygen supply is sufficient. In addition, deregulated anabolism/catabolism of fatty acids and amino acids, especially glutamine, serine and glycine, have been identified to function as metabolic regulators in supporting cancer cell growth. Furthermore, extensive crosstalks are being revealed between the deregulated metabolic network and cancer cell signaling. These exciting advancements have inspired new strategies for treating various malignancies by targeting cancer metabolism. Here we review recent findings related to the regulation of glucose, fatty acid and amino acid metabolism, their crosstalk, and relevant cancer therapy strategy.
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                Author and article information

                Contributors
                yangqing_sj@126.com
                Journal
                Mol Cancer
                Molecular Cancer
                BioMed Central (London )
                1476-4598
                1 October 2020
                1 October 2020
                2020
                : 19
                : 146
                Affiliations
                [1 ]GRID grid.412467.2, ISNI 0000 0004 1806 3501, Department of Obstetrics and Gynecology, , Shengjing Hospital of China Medical University, ; No. 36, Sanhao Street, Heping District, Shenyang, 110004 China
                [2 ]GRID grid.412636.4, Department of Urology, , First Hospital of China Medical University, ; Shenyang, China
                Author information
                http://orcid.org/0000-0002-6379-7577
                Article
                1262
                10.1186/s12943-020-01262-x
                7529510
                33004065
                d5a282d1-45d7-4754-ac1c-0aadb4bcb6e2
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 15 July 2020
                : 23 September 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81872125
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2020

                Oncology & Radiotherapy
                ubiquitination,deubiquitination,cancer,metabolic reprogramming
                Oncology & Radiotherapy
                ubiquitination, deubiquitination, cancer, metabolic reprogramming

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