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: BACKGROUND Multiple myeloma ( MM ) is a fatal plasma cell malignancy exhibiting enhanced glucose consumption associated with an aerobic glycolytic phenotype ( i.e. , the Warburg effect ) . We have previously demonstrated that myeloma cells exhibit constitutive plasma membrane ( PM ) localization of GLUT4 , consistent with the dependence of MM cells on this transporter for maintenance of glucose consumption rates , proliferative capacity , and viability . The purpose of this study was to investigate the molecular basis of constitutive GLUT4 plasma membrane localization in MM cells . FINDINGS We have elucidated a novel mechanism through which myeloma cells achieve constitutive GLUT4 activation involving elevated expression of the Rab-GTPase activating protein AS160_v2 splice variant to promote the Warburg effect . AS160_v2-positive MM cell lines display constitutive Thr642 phosphorylation , known to be required for inactivation of AS160 Rab-GAP activity . Importantly , we show that enforced expression of AS160_v2 is required for GLUT4 PM translocation and activation in these select MM lines . Furthermore , we demonstrate that ectopic expression of a full-length , phospho-deficient AS160 mutant is sufficient to impair constitutive GLUT4 cell surface residence , which is characteristic of MM cells . CONCLUSIONS This is the first study to tie AS160 de-regulation to increased glucose consumption rates and the Warburg effect in cancer . Future studies investigating connections between the insulin/IGF-1/AS160_v2/GLUT4 axis and FDG-PET positivity in myeloma patients are warranted and could provide rationale for therapeutically targeting this pathway in MM patients with advanced disease .
    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.
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    INPUT: BACKGROUND Multiple myeloma ( MM ) is a fatal plasma cell malignancy exhibiting enhanced glucose consumption associated with an aerobic glycolytic phenotype ( i.e. , the Warburg effect ) . We have previously demonstrated that myeloma cells exhibit constitutive plasma membrane ( PM ) localization of GLUT4 , consistent with the dependence of MM cells on this transporter for maintenance of glucose consumption rates , proliferative capacity , and viability . The purpose of this study was to investigate the molecular basis of constitutive GLUT4 plasma membrane localization in MM cells . FINDINGS We have elucidated a novel mechanism through which myeloma cells achieve constitutive GLUT4 activation involving elevated expression of the Rab-GTPase activating protein AS160_v2 splice variant to promote the Warburg effect . AS160_v2-positive MM cell lines display constitutive Thr642 phosphorylation , known to be required for inactivation of AS160 Rab-GAP activity . Importantly , we show that enforced expression of AS160_v2 is required for GLUT4 PM translocation and activation in these select MM lines . Furthermore , we demonstrate that ectopic expression of a full-length , phospho-deficient AS160 mutant is sufficient to impair constitutive GLUT4 cell surface residence , which is characteristic of MM cells . CONCLUSIONS This is the first study to tie AS160 de-regulation to increased glucose consumption rates and the Warburg effect in cancer . Future studies investigating connections between the insulin/IGF-1/AS160_v2/GLUT4 axis and FDG-PET positivity in myeloma patients are warranted and could provide rationale for therapeutically targeting this pathway in MM patients with advanced disease .
    OUTPUT:
