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      Targeting Cellular Metabolism Modulates Head and Neck Oncogenesis

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          Abstract

          Considering the great energy and biomass demand for cell survival, cancer cells exhibit unique metabolic signatures compared to normal cells. Head and neck squamous cell carcinoma (HNSCC) is one of the most prevalent neoplasms worldwide. Recent findings have shown that environmental challenges, as well as intrinsic metabolic manipulations, could modulate HNSCC experimentally and serve as clinic prognostic indicators, suggesting that a better understanding of dynamic metabolic changes during HNSCC development could be of great benefit for developing adjuvant anti-cancer schemes other than conventional therapies. However, the following questions are still poorly understood: (i) how does metabolic reprogramming occur during HNSCC development? (ii) how does the tumorous milieu contribute to HNSCC tumourigenesis? and (iii) at the molecular level, how do various metabolic cues interact with each other to control the oncogenicity and therapeutic sensitivity of HNSCC? In this review article, the regulatory roles of different metabolic pathways in HNSCC and its microenvironment in controlling the malignancy are therefore discussed in the hope of providing a systemic overview regarding what we knew and how cancer metabolism could be translated for the development of anti-cancer therapeutic reagents.

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          Most cited references178

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          On the origin of cancer cells.

          O WARBURG (1956)
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            The transcriptional landscape of the mammalian genome.

            This study describes comprehensive polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome. We identify the 5' and 3' boundaries of 181,047 transcripts with extensive variation in transcripts arising from alternative promoter usage, splicing, and polyadenylation. There are 16,247 new mouse protein-coding transcripts, including 5154 encoding previously unidentified proteins. Genomic mapping of the transcriptome reveals transcriptional forests, with overlapping transcription on both strands, separated by deserts in which few transcripts are observed. The data provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.
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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

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                14 August 2019
                August 2019
                : 20
                : 16
                : 3960
                Affiliations
                [1 ]Institute of Oral Biology, School of Dentistry, National Yang-Ming University, Taipei 11221, Taiwan
                [2 ]Department of Dentistry, School of Dentistry, National Yang-Ming University, Taipei 11221, Taiwan
                [3 ]Department of Stomatology, Taipei Veterans General Hospital, Taipei 11217, Taiwan
                [4 ]Cancer Progression Research Center, National Yang-Ming University, Taipei 11221, Taiwan
                Author notes
                [* ]Correspondence: wcli@ 123456ym.edu.tw ; Tel.: +886-2-2826-7255; Fax: +886-2-2826-4053
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0001-9177-3647
                https://orcid.org/0000-0003-0481-4215
                Article
                ijms-20-03960
                10.3390/ijms20163960
                6721038
                31416244
                f5ec53fd-89c4-4e64-8c09-c86139e4323f
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 01 August 2019
                : 13 August 2019
                Categories
                Review

                Molecular biology
                head and neck cancer,metabolic reprogramming,tumor microenvironment,non-coding rna,targeted therapy

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