Repressing malic enzyme 1 redirects glucose metabolism, unbalances the redox state, and attenuates migratory and invasive abilities in nasopharyngeal carcinoma cell lines

• Published in: Ai zheng Vol. 31; no. 11; pp. 519 - 531
• Main Authors: Zheng, Fang-Jing, Ye, Hao-Bin, Wu, Man-Si, Lian, Yi-Fan, Qian, Chao-Nan, Zeng, Yi-Xin
• Format: Journal Article
• Language: English
• Published: England Department of Experimental Research,Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P.R.China 01.11.2012; Department of Nasopharyngeal Carcinoma,Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P.R.China; State Key Laboratory of Oncology in South China,Guangzhou, Guangdong 510060, P.R.China; Department of Experimental Research,Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P.R.China%State Key Laboratory of Oncology in South China,Guangzhou, Guangdong 510060, P.R.China; Department of Pathology, University of Rochester Medical Center,Rochester, NY, USA%State Key Laboratory of Oncology in South China,Guangzhou, Guangdong 510060, P.R.China; Sun Yat-sen University Cancer Center
• Subjects: Carcinoma; Cell Line, Tumor; Cell Movement; Cell Survival; Glucose - metabolism; Glycolysis; Humans; Malate Dehydrogenase - metabolism; NADP - metabolism; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms - metabolism; Nasopharyngeal Neoplasms - pathology; Neoplasm Invasiveness; Original; Oxidation-Reduction; Oxidative Phosphorylation; Pentose Phosphate Pathway; Proto-Oncogene Proteins c-akt - metabolism; Nasopharyngeal carcinoma; NADPH; malic enzyme 1; low glucose
• ISSN: 1000-467X; 1944-446X
• DOI: 10.5732/cjc.012.10088

A large amount of nicotinamide adenine dinucleotide phosphate (NADPH) is required for fatty acid synthesis and maintenance of the redox state in cancer cells. Malic enzyme 1(ME1)-dependent NADPH production is one of the three pathways that contribute to the formation of the cytosolic NADPH pool. ME1 is generally considered to be overexpressed in cancer cells to meet the high demand for increased de novo fatty acid synthesis. In the present study, we found that glucose induced higher ME1 activity and that repressing ME1 had a profound impact on glucose metabolism of nasopharyngeal carcinoma(NPC) cells. High incorporation of glucose and an enhancement of the pentose phosphate pathway were observed in ME1-repressed cells. However, there were no obvious changes in the other two pathways for glucose metabolism: glycolysis and oxidative phosphorylation. Interestingly, NADPH was decreased under low-glucose condition in ME1-repressed cells relative to wild-type cells, whereas no significant difference was observed under high-glucose condition. ME1-repressed cells had significantly decreased tolerance to low-glucose condition. Moreover, NADPH produced by ME1 was not only important for fatty acid synthesis but also essential for maintenance of the intracellular redox state and the protection of cells from oxidative stress. Furthermore, diminished migration and invasion were observed in ME1-repressed cells due to a reduced level of Snail protein. Collectively, these results suggest an essential role for ME1 in the production of cytosolic NADPH and maintenance of migratory and invasive abilities of NPC cells.