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.
    ###
    INPUT: Cav-1 ( -/- ) deficient stromal cells are a new genetic model for myofibroblasts and cancer-associated fibroblasts . Using an unbiased informatics analysis of the transcriptional profile of Cav-1 ( -/- ) deficient mesenchymal stromal cells , we have now identified many of the major signaling pathways that are activated by a loss of Cav-1 , under conditions of metabolic restriction ( with low glucose media ) . Our informatics analysis suggests that a loss of Cav-1 induces oxidative stress , which mimics a constitutive pseudo-hypoxic state , leading to ( 1 ) aerobic glycolysis and ( 2 ) inflammation in the tumor stromal microenvironment . This occurs via the activation of two major transcription factors , namely HIF ( aerobic glycolysis ) and NFÎºB ( inflammation ) in Cav-1 ( -/- ) stromal fibroblastic cells . Experimentally , we show that Cav-1 deficient stromal cells may possess defective mitochondria , due to the over-production of nitric oxide ( NO ) , resulting in the tyrosine nitration of the mitochondrial respiratory chain components ( such as complex I ) . Elevated levels of nitro-tyrosine were observed both in Cav-1 ( -/- ) stromal cells , and via acute knock-down with siRNA targeting Cav-1 . Finally , metabolic restriction with mitochondrial ( complex I ) and glycolysis inhibitors was synthetically lethal with a Cav-1 ( -/- ) deficiency in mice . As such , Cav-1 deficient mice show a dramatically reduced mitochondrial reserve capacity . Thus , a mitochondrial defect in Cav-1 deficient stromal cells could drive oxidative stress , leading to aerobic glycolysis , and inflammation , in the tumor microenvironment . These stromal alterations may underlie the molecular basis of the " reverse Warburg effect " , and could provide the key to targeted anti-cancer therapies using metabolic inhibitors . In direct support of these findings , the transcriptional profile of Cav-1 ( -/- ) stromal cells overlaps significantly with Alzheimer disease , which is characterized by oxidative stress , NO over-production ( peroxynitrite formation ) , inflammation , hypoxia and mitochondrial dysfunction . We conclude that Cav-1 ( -/- ) deficient mice are a new whole-body animal model for an activated lethal tumor microenvironment , i.e. , " tumor stroma " without the tumor . Since Cav-1 ( -/- ) mice are also an established animal model for profibrotic disease , our current results may have implications for understanding the pathogenesis of scleroderma ( systemic sclerosis ) and pulmonary fibrosis , which are also related to abnormal mesenchymal stem cell function .
    OUTPUT:

agent
tumor promoting inflammation;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: Cav-1 ( -/- ) deficient stromal cells are a new genetic model for myofibroblasts and cancer-associated fibroblasts . Using an unbiased informatics analysis of the transcriptional profile of Cav-1 ( -/- ) deficient mesenchymal stromal cells , we have now identified many of the major signaling pathways that are activated by a loss of Cav-1 , under conditions of metabolic restriction ( with low glucose media ) . Our informatics analysis suggests that a loss of Cav-1 induces oxidative stress , which mimics a constitutive pseudo-hypoxic state , leading to ( 1 ) aerobic glycolysis and ( 2 ) inflammation in the tumor stromal microenvironment . This occurs via the activation of two major transcription factors , namely HIF ( aerobic glycolysis ) and NFÎºB ( inflammation ) in Cav-1 ( -/- ) stromal fibroblastic cells . Experimentally , we show that Cav-1 deficient stromal cells may possess defective mitochondria , due to the over-production of nitric oxide ( NO ) , resulting in the tyrosine nitration of the mitochondrial respiratory chain components ( such as complex I ) . Elevated levels of nitro-tyrosine were observed both in Cav-1 ( -/- ) stromal cells , and via acute knock-down with siRNA targeting Cav-1 . Finally , metabolic restriction with mitochondrial ( complex I ) and glycolysis inhibitors was synthetically lethal with a Cav-1 ( -/- ) deficiency in mice . As such , Cav-1 deficient mice show a dramatically reduced mitochondrial reserve capacity . Thus , a mitochondrial defect in Cav-1 deficient stromal cells could drive oxidative stress , leading to aerobic glycolysis , and inflammation , in the tumor microenvironment . These stromal alterations may underlie the molecular basis of the " reverse Warburg effect " , and could provide the key to targeted anti-cancer therapies using metabolic inhibitors . In direct support of these findings , the transcriptional profile of Cav-1 ( -/- ) stromal cells overlaps significantly with Alzheimer disease , which is characterized by oxidative stress , NO over-production ( peroxynitrite formation ) , inflammation , hypoxia and mitochondrial dysfunction . We conclude that Cav-1 ( -/- ) deficient mice are a new whole-body animal model for an activated lethal tumor microenvironment , i.e. , " tumor stroma " without the tumor . Since Cav-1 ( -/- ) mice are also an established animal model for profibrotic disease , our current results may have implications for understanding the pathogenesis of scleroderma ( systemic sclerosis ) and pulmonary fibrosis , which are also related to abnormal mesenchymal stem cell function .
    OUTPUT:
