title: Nutrient deprivation-related OXPHOS/glycolysis interconversion via HIF-1α/C-MYC pathway in U251 cells.
abstract: Although the Warburg effect is a dominant metabolic phenotype observed in cancers, the metabolic changes and adaptation occurring in tumors have been demonstrated to extend beyond the Warburg effect and thus considered a secondary effect to the transformation process of carcinogenesis, including nutritional deficiencies. However, the role of nutritional deficiencies in this metabolic reprogramming (e. g., oxidative phosphorylation (OXPHOS)/glycolysis interconversion) is not completely known yet. Here, we showed that under regular culture condition, the proliferation of U251 cells, but not other tumor cell lines, preferentially performed the Warburg effect and was remarkably inhibited by oxamic acid which can inhibit the activity of lactate dehydrogenase (LDH); whereas under serum starvation, glycolysis was depressed, tricarboxylic acid cycle (TCA) was enhanced, and the activity of OXPHOS was reinforced to maintain cellular ATP content in a high level, but interestingly, we observed a decreased expression of reactive oxygen species (ROS). Moreover, the upregulated activity of mitochondrial complex I was confirmed by Western blots and showed that the mitochondrial-related protein, NDUFA9, NDUFB8, ND1, and VDAC1 were remarkably increased after serum starved. Mechanistically, nutritional deficiencies could reduce hypoxia-inducible factor α (HIF-1α) protein expression to increase C-MYC protein level, which in turn increased nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM) transcription to enhance the activity of OXPHOS, suggesting that metabolic reprogramming by the changes of microenvironment during the carcinogenesis can provide some novel therapeutic clues to traditional cancer treatments.
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, School of Life Sciences, Yunnan University, Kunming, 650091, China.|Key Laboratory for Molecular Biology of High Education in Yunnan Province, School of Life Sciences, Yunnan University, Kunming, 650091, China.|Department of Biochemistry and Molecular Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, 610041, China.
authors.forename: Zhongjian
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, School of Life Sciences, Yunnan University, Kunming, 650091, China.|Key Laboratory for Molecular Biology of High Education in Yunnan Province, School of Life Sciences, Yunnan University, Kunming, 650091, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, School of Life Sciences, Yunnan University, Kunming, 650091, China.|Key Laboratory for Molecular Biology of High Education in Yunnan Province, School of Life Sciences, Yunnan University, Kunming, 650091, China.
authors.forename: Shirui
authors.initials: S
authors.lastname: Tan
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, School of Life Sciences, Yunnan University, Kunming, 650091, China.|Key Laboratory for Molecular Biology of High Education in Yunnan Province, School of Life Sciences, Yunnan University, Kunming, 650091, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Liu
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, School of Life Sciences, Yunnan University, Kunming, 650091, China.|Key Laboratory for Molecular Biology of High Education in Yunnan Province, School of Life Sciences, Yunnan University, Kunming, 650091, China.
authors.forename: Suqiong
authors.initials: S
authors.lastname: Hu
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, School of Life Sciences, Yunnan University, Kunming, 650091, China.|Key Laboratory for Molecular Biology of High Education in Yunnan Province, School of Life Sciences, Yunnan University, Kunming, 650091, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Huo
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, School of Life Sciences, Yunnan University, Kunming, 650091, China.|Key Laboratory for Molecular Biology of High Education in Yunnan Province, School of Life Sciences, Yunnan University, Kunming, 650091, China.
authors.forename: Meizhang
authors.initials: M
authors.lastname: Li
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, School of Life Sciences, Yunnan University, Kunming, 650091, China.|Key Laboratory for Molecular Biology of High Education in Yunnan Province, School of Life Sciences, Yunnan University, Kunming, 650091, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Cui
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, School of Life Sciences, Yunnan University, Kunming, 650091, China. yumin@ynu.edu.cn.|Key Laboratory for Molecular Biology of High Education in Yunnan Province, School of Life Sciences, Yunnan University, Kunming, 650091, China. yumin@ynu.edu.cn.
authors.forename: Min
authors.initials: M
authors.lastname: Yu
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002952:Citric Acid Cycle; D004734:Energy Metabolism; D006019:Glycolysis; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D053858:Metabolic Networks and Pathways; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D010085:Oxidative Phosphorylation; D010641:Phenotype; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D015398:Signal Transduction; D013217:Starvation / Q000378:metabolism
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016271:Proto-Oncogene Proteins c-myc; D000255:Adenosine Triphosphate
keywords: C-MYC; Glycolysis; HIF-1α; OXPHOS; Starvation