https://scholars.lib.ntu.edu.tw/handle/123456789/584964
標題: | Determination of Pyruvate Metabolic Fates Modulates Head and Neck Tumorigenesis | 作者: | Chen T.-Y. Hsieh Y.-T. Huang J.-M. Liu C.-J. Chuang L.-T. Huang P.-C. Kuo T.-Y. Chia H.-Y. Chou C.-Y. Chang C.-W. Chen Y.-F. HSIN-MING CHEN Lo J.-F. Li W.-C. |
公開日期: | 2019 | 出版社: | Neoplasia Press, Inc. | 卷: | 21 | 期: | 7 | 起(迄)頁: | 641-652 | 來源出版物: | Neoplasia (United States) | 摘要: | Even with increasing evidence for roles of glycolytic enzymes in controlling cancerous characteristics, the best target of candidate metabolic enzymes for lessening malignancy remains under debate. Pyruvate is a main glycolytic metabolite that could be mainly converted into either lactate by Lactate Dehydrogenase A (LDHA)or acetyl-CoA by Pyruvate Dehydrogenase E1 component α subunit (PDHA1)catalytic complex. In tumor cells, accumulating lactate is produced whereas the conversion of pyruvate into mitochondrial acetyl-CoA is less active compared with their normal counterparts. This reciprocal molecular association makes pyruvate metabolism a potential choice of anti-cancer target. Cellular and molecular changes were herein assayed in Head and Neck Squamous Cell Carcinoma (HNSCC)cells in response to LDHA and PDHA1 loss in vitro, in vivo and in clinic. By using various human cancer databases and clinical samples, LDHA and PDHA1 levels exhibit reversed prognostic roles. In vitro analysis demonstrated that decreased cell growth and motility accompanied by an increased sensitivity to chemotherapeutic agents was found in cells with LDHA loss whereas PDHA1-silencing exhibited opposite phenotypes. At the molecular level, it was found that oncogenic Protein kinase B (PKB/Akt)and Extracellular signal-regulated kinase (ERK)singling pathways contribute to pyruvate metabolism mediated HNSCC cell growth. Furthermore, LDHA/PDHA1 changes in HNSCC cells resulted in a broad metabolic reprogramming while intracellular molecules including polyunsaturated fatty acids and nitrogen metabolism related metabolites underlie the malignant changes. Collectively, our findings reveal the significance of pyruvate metabolic fates in modulating HNSCC tumorigenesis and highlight the impact of metabolic plasticity in HNSCC cells. ? 2019 The Authors |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85065532617&doi=10.1016%2fj.neo.2019.04.007&partnerID=40&md5=17a0178990b883f3b5afe094c5572aec https://scholars.lib.ntu.edu.tw/handle/123456789/584964 |
ISSN: | 1522-8002 | DOI: | 10.1016/j.neo.2019.04.007 | SDG/關鍵字: | lactate dehydrogenase; lactate dehydrogenase A; mitogen activated protein kinase; protein kinase B; pyruvate dehydrogenase; pyruvate dehydrogenase E1 component alpha; pyruvic acid; unclassified drug; lactate dehydrogenase; lactic acid; LDHA protein, human; pyruvate dehydrogenase; pyruvate dehydrogenase E1alpha subunit; pyruvic acid; Akt signaling; animal experiment; animal model; animal tissue; Article; cancer prognosis; carcinogenesis; cell differentiation; cell growth; cell motility; controlled study; gene silencing; head and neck squamous cell carcinoma; human; human cell; human tissue; in vitro study; in vivo study; MAPK signaling; metabolism; mouse; nonhuman; nuclear reprogramming; priority journal; protein depletion; protein expression; animal; cell proliferation; genetics; glycolysis; metabolism; mitochondrion; pathology; tumor cell line; xenograft; Animals; Carcinogenesis; Cell Line, Tumor; Cell Proliferation; Glycolysis; Heterografts; Humans; L-Lactate Dehydrogenase; Lactic Acid; Mice; Mitochondria; Pyruvate Dehydrogenase (Lipoamide); Pyruvic Acid; Squamous Cell Carcinoma of Head and Neck |
顯示於: | 牙醫學系 |
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