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10.1016/j.cmet.2016.09.006 http://scihub22266oqcxt.onion/10.1016/j.cmet.2016.09.006 C5102768!5102768 !27746050     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=27746050 &cmd=llinks): Failed to open stream: HTTP request failed! 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Environment Dictates Dependence on Mitochondrial Complex I for NAD+ and Aspartate Production and Determines Cancer Cell Sensitivity to Metformin |pdf=|usr=}}{{27746050 }} gab.com Text Environment Dictates Dependence on Mitochondrial Complex I for NAD+ and Aspartate Production and Determines Cancer Cell Sensitivity to Metformin JO: Cell Metab http://www.kidney.de/pget.php?&tw=1&pmid=27746050 #FOAvip Metformin use is associated with reduced cancer mortality, but how metformin impacts cancer outcomes is controversial. Although metformin can act on cells autonomously to inhibit tumor growth, the doses of metformin that inhibit proliferation in tissue culture are much higher than what has been described in vivo. Here, we show that the environment drastically alters sensitivity to metformin and other complex I inhibitors. We find that complex I supports proliferation by regenerating nicotinamide adenine dinucleotide (NAD)+, and metformin's anti-proliferative effect is due to loss of NAD+/NADH homeostasis and inhibition of aspartate biosynthesis. However, complex I is only one of many inputs that determines the cellular NAD+/NADH ratio, and dependency on complex I is dictated by the activity of other pathways that affect NAD+ regeneration and aspartate levels. This suggests that cancer drug sensitivity and resistance are not intrinsic properties of cancer cells, and demonstrates that the environment can dictate sensitivity to therapies that impact cell metabolism. Twit Text FOAVip Environment Dictates Dependence on Mitochondrial Complex I for NAD+ and Aspartate Production and Determines Cancer Cell Sensitivity to Metformin ????Cell Metab http://www.kidney.de/pget.php?&tw=1&pmid=27746050 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=27746050 #FOAvip English Wikipedia <ref>{{Cite pmid|27746050 }}</ref> Environment Dictates Dependence on Mitochondrial Complex I for NAD+ and Aspartate Production and Determines Cancer Cell Sensitivity to Metformin #MMPMID27746050 Gui DY ; Sullivan LB ; Luengo A ; Hosios AM ; Bush LN ; Gitego N ; Davidson SM ; Freinkman E ; Thomas CJ ; Vander Heiden MG Cell Metab 2016[Nov]; 24 (5 ): 716-727 PMID27746050 show ga Metformin use is associated with reduced cancer mortality, but how metformin impacts cancer outcomes is controversial. Although metformin can act on cells autonomously to inhibit tumor growth, the doses of metformin that inhibit proliferation in tissue culture are much higher than what has been described in vivo. Here, we show that the environment drastically alters sensitivity to metformin and other complex I inhibitors. We find that complex I supports proliferation by regenerating nicotinamide adenine dinucleotide (NAD)+, and metformin's anti-proliferative effect is due to loss of NAD+/NADH homeostasis and inhibition of aspartate biosynthesis. However, complex I is only one of many inputs that determines the cellular NAD+/NADH ratio, and dependency on complex I is dictated by the activity of other pathways that affect NAD+ regeneration and aspartate levels. This suggests that cancer drug sensitivity and resistance are not intrinsic properties of cancer cells, and demonstrates that the environment can dictate sensitivity to therapies that impact cell metabolism. |Animals [MESH] |Aspartic Acid/*biosynthesis [MESH] |Cell Line, Tumor [MESH] |Cell Proliferation/drug effects [MESH] |Electron Transport Complex I/*metabolism [MESH] |Homeostasis/drug effects [MESH] |Humans [MESH] |Metformin/*pharmacology [MESH] |Mice, Nude [MESH] |Mitochondria/drug effects/*metabolism [MESH] |NAD/*metabolism [MESH] |Neoplasms/*pathology [MESH] |Pyruvic Acid/pharmacology [MESH]Environment Dictates Dependence on Mitochondrial Complex I for NAD+ an(epmc).pdf DeepDyve Pubget Overpricing