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Novel role of NOX in supporting aerobic glycolysis in cancer cells with mitochondrial dysfunction and as a potential target for cancer therapy
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نویسنده
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lu w. ,hu y. ,chen g. ,chen z. ,zhang h. ,wang f. ,feng l. ,pelicano h. ,wang h. ,keating m.j. ,liu j. ,mckeehan w. ,wang h. ,luo y. ,huang p.
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منبع
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plos biology - 2012 - دوره : 10 - شماره : 5
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چکیده
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Elevated aerobic glycolysis in cancer cells (the warburg effect) may be attributed to respiration injury or mitochondrial dysfunction,but the underlying mechanisms and therapeutic significance remain elusive. here we report that induction of mitochondrial respiratory defect by tetracycline-controlled expression of a dominant negative form of dna polymerase γ causes a metabolic shift from oxidative phosphorylation to glycolysis and increases ros generation. we show that upregulation of nox is critical to support the elevated glycolysis by providing additional nad+. the upregulation of nox is also consistently observed in cancer cells with compromised mitochondria due to the activation of oncogenic ras or loss of p53,and in primary pancreatic cancer tissues. suppression of nox by chemical inhibition or genetic knockdown of gene expression selectively impacts cancer cells with mitochondrial dysfunction,leading to a decrease in cellular glycolysis,a loss of cell viability,and inhibition of cancer growth in vivo. our study reveals a previously unrecognized function of nox in cancer metabolism and suggests that nox is a potential novel target for cancer treatment. © 2012 lu et al.
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آدرس
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department of molecular pathology,the university of texas md anderson cancer center,houston,tx, United States, department of molecular pathology,the university of texas md anderson cancer center,houston,tx,united states,state key laboratory of oncology in southern china,sun yat-sen university cancer center,guangzhou, China, department of molecular pathology,the university of texas md anderson cancer center,houston,tx, United States, department of molecular pathology,the university of texas md anderson cancer center,houston,tx, United States, department of molecular pathology,the university of texas md anderson cancer center,houston,tx, United States, department of molecular pathology,the university of texas md anderson cancer center,houston,tx,united states,state key laboratory of oncology in southern china,sun yat-sen university cancer center,guangzhou, China, department of molecular pathology,the university of texas md anderson cancer center,houston,tx, United States, department of molecular pathology,the university of texas md anderson cancer center,houston,tx, United States, department of gi medical oncology,the university of texas md anderson cancer center,houston,tx, United States, department of leukemia,the university of texas md anderson cancer center,houston,tx, United States, department of pathology,the university of texas md anderson cancer center,houston,tx, United States, proteomics and nanotechnology laboratory,center for cancer and stem cell biology,institute of biosciences and technology,texas a and m university health science center,houston,tx, United States, department of pathology,the university of texas md anderson cancer center,houston,tx, United States, proteomics and nanotechnology laboratory,center for cancer and stem cell biology,institute of biosciences and technology,texas a and m university health science center,houston,tx, United States, department of molecular pathology,the university of texas md anderson cancer center,houston,tx, United States
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Authors
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