Repressing malic enzyme 1 unbalances the redox state, redirects glucose metabolism, and attenuates migratory and invasive abilities in nasopharyngeal carcinoma cell lines
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. ME...
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Veröffentlicht in: | 癌症:英文版 2012, Vol.31 (11), p.519-531 |
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Sprache: | eng |
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Zusammenfassung: | 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 MEl-repressed cells. However, there were no obvious changes in the other two pathways for glucose metabolism: gtycotysis and oxidative phosphorylation. Interestingly, NADPH was decreased under low- glucose condition in MEl-repressed cells relative to wild-type cells, whereas no significant difference was observed under high-glucose condition. MEl-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 MEl-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. |
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ISSN: | 1000-467X 1944-446X |