human
The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
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    INPUT: P53 has an important role in the processing of starvation signals . P53-dependent molecular mediators of the Warburg effect reduce glucose consumption and promote mitochondrial function . We therefore hypothesized that the retention of wild-type p53 characteristic of primary glioblastomas limits metabolic demands induced by deregulated signal transduction in the presence of hypoxia and nutrient depletion . Here we report that short hairpin RNA-mediated gene suppression of wild-type p53 or ectopic expression of mutant temperature-sensitive dominant-negative p53(V135A) increased glucose consumption and lactate production , decreased oxygen consumption and enhanced hypoxia-induced cell death in p53 wild-type human glioblastoma cells . Similarly , genetic knockout of p53 in HCT116 colon carcinoma cells resulted in reduced respiration and hypersensitivity towards hypoxia-induced cell death . Further , wild-type p53 gene silencing reduced the expression of synthesis of cytochrome c oxidase 2 ( SCO2 ) , an effector necessary for respiratory chain function . An SCO2 transgene reverted the metabolic phenotype and restored resistance towards hypoxia in p53-depleted and p53 mutant glioma cells in a rotenone-sensitive manner , demonstrating that this effect was dependent on intact oxidative phosphorylation . Supplementation with methyl-pyruvate , a mitochondrial substrate , rescued p53 wild-type but not p53 mutant cells from hypoxic cell death , demonstrating a p53-mediated selective aptitude to metabolize mitochondrial substrates . Further , SCO2 gene silencing in p53 wild-type glioma cells sensitized these cells towards hypoxia . Finally , lentiviral gene suppression of SCO2 significantly enhanced tumor necrosis in a subcutaneous HCT116 xenograft tumor model , compatible with impaired energy metabolism in these cells . These findings demonstrate that glioma and colon cancer cells with p53 wild-type status can skew the Warburg effect and thereby reduce their vulnerability towards tumor hypoxia in an SCO2-dependent manner . Targeting SCO2 may therefore represent a valuable strategy to enhance sensitivity towards hypoxia and may complement strategies targeting glucose metabolism .
    OUTPUT:

agent
cellular energetics
The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
    ###
    INPUT: P53 has an important role in the processing of starvation signals . P53-dependent molecular mediators of the Warburg effect reduce glucose consumption and promote mitochondrial function . We therefore hypothesized that the retention of wild-type p53 characteristic of primary glioblastomas limits metabolic demands induced by deregulated signal transduction in the presence of hypoxia and nutrient depletion . Here we report that short hairpin RNA-mediated gene suppression of wild-type p53 or ectopic expression of mutant temperature-sensitive dominant-negative p53(V135A) increased glucose consumption and lactate production , decreased oxygen consumption and enhanced hypoxia-induced cell death in p53 wild-type human glioblastoma cells . Similarly , genetic knockout of p53 in HCT116 colon carcinoma cells resulted in reduced respiration and hypersensitivity towards hypoxia-induced cell death . Further , wild-type p53 gene silencing reduced the expression of synthesis of cytochrome c oxidase 2 ( SCO2 ) , an effector necessary for respiratory chain function . An SCO2 transgene reverted the metabolic phenotype and restored resistance towards hypoxia in p53-depleted and p53 mutant glioma cells in a rotenone-sensitive manner , demonstrating that this effect was dependent on intact oxidative phosphorylation . Supplementation with methyl-pyruvate , a mitochondrial substrate , rescued p53 wild-type but not p53 mutant cells from hypoxic cell death , demonstrating a p53-mediated selective aptitude to metabolize mitochondrial substrates . Further , SCO2 gene silencing in p53 wild-type glioma cells sensitized these cells towards hypoxia . Finally , lentiviral gene suppression of SCO2 significantly enhanced tumor necrosis in a subcutaneous HCT116 xenograft tumor model , compatible with impaired energy metabolism in these cells . These findings demonstrate that glioma and colon cancer cells with p53 wild-type status can skew the Warburg effect and thereby reduce their vulnerability towards tumor hypoxia in an SCO2-dependent manner . Targeting SCO2 may therefore represent a valuable strategy to enhance sensitivity towards hypoxia and may complement strategies targeting glucose metabolism .
    OUTPUT:
