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 NFÎºB signaling is of paramount importance in the regulation of apoptosis , proliferation , and inflammatory responses during human development and homeostasis , as well as in many human cancers . Receptor Tyrosine Kinases ( RTKs ) , including the Fibroblast Growth Factor Receptors ( FGFRs ) are also important in development and disease . However , a direct relationship between growth factor signaling pathways and NFÎºB activation has not been previously described , although FGFs have been known to antagonize TNFÎ±-induced apoptosis . METHODOLOGY/PRINCIPAL FINDINGS Here , we demonstrate an interaction between FGFR4 and IKKÎ² ( Inhibitor of NFÎºB Kinase Î² subunit ) , an essential component in the NFÎºB pathway . This novel interaction was identified utilizing a yeast two-hybrid screen [ 1 ] and confirmed by coimmunoprecipitation and mass spectrometry analysis . We demonstrate tyrosine phosphorylation of IKKÎ² in the presence of activated FGFR4 , but not kinase-dead FGFR4 . Following stimulation by TNFÎ± ( Tumor Necrosis Factor Î± ) to activate NFÎºB pathways , FGFR4 activation results in significant inhibition of NFÎºB signaling as measured by decreased nuclear NFÎºB localization , by reduced NFÎºB transcriptional activation in electophoretic mobility shift assays , and by inhibition of IKKÎ² kinase activity towards the substrate GST-IÎºBÎ± in in vitro assays . FGF19 stimulation of endogenous FGFR4 in TNFÎ±-treated DU145 prostate cancer cells also leads to a decrease in IKKÎ² activity , concomitant reduction in NFÎºB nuclear localization , and reduced apoptosis . Microarray analysis demonstrates that FGF19 + TNFÎ± treatment of DU145 cells , in comparison with TNFÎ± alone , favors proliferative genes while downregulating genes involved in apoptotic responses and NFÎºB signaling . CONCLUSIONS/SIGNIFICANCE These results identify a compelling link between FGFR4 signaling and the NFÎºB pathway , and reveal that FGFR4 activation leads to a negative effect on NFÎºB signaling including an inhibitory effect on proapoptotic signaling . We anticipate that this interaction between an RTK and a component of NFÎºB signaling will not be limited to FGFR4 alone .
    OUTPUT:

agent
sustaining proliferative signaling
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 NFÎºB signaling is of paramount importance in the regulation of apoptosis , proliferation , and inflammatory responses during human development and homeostasis , as well as in many human cancers . Receptor Tyrosine Kinases ( RTKs ) , including the Fibroblast Growth Factor Receptors ( FGFRs ) are also important in development and disease . However , a direct relationship between growth factor signaling pathways and NFÎºB activation has not been previously described , although FGFs have been known to antagonize TNFÎ±-induced apoptosis . METHODOLOGY/PRINCIPAL FINDINGS Here , we demonstrate an interaction between FGFR4 and IKKÎ² ( Inhibitor of NFÎºB Kinase Î² subunit ) , an essential component in the NFÎºB pathway . This novel interaction was identified utilizing a yeast two-hybrid screen [ 1 ] and confirmed by coimmunoprecipitation and mass spectrometry analysis . We demonstrate tyrosine phosphorylation of IKKÎ² in the presence of activated FGFR4 , but not kinase-dead FGFR4 . Following stimulation by TNFÎ± ( Tumor Necrosis Factor Î± ) to activate NFÎºB pathways , FGFR4 activation results in significant inhibition of NFÎºB signaling as measured by decreased nuclear NFÎºB localization , by reduced NFÎºB transcriptional activation in electophoretic mobility shift assays , and by inhibition of IKKÎ² kinase activity towards the substrate GST-IÎºBÎ± in in vitro assays . FGF19 stimulation of endogenous FGFR4 in TNFÎ±-treated DU145 prostate cancer cells also leads to a decrease in IKKÎ² activity , concomitant reduction in NFÎºB nuclear localization , and reduced apoptosis . Microarray analysis demonstrates that FGF19 + TNFÎ± treatment of DU145 cells , in comparison with TNFÎ± alone , favors proliferative genes while downregulating genes involved in apoptotic responses and NFÎºB signaling . CONCLUSIONS/SIGNIFICANCE These results identify a compelling link between FGFR4 signaling and the NFÎºB pathway , and reveal that FGFR4 activation leads to a negative effect on NFÎºB signaling including an inhibitory effect on proapoptotic signaling . We anticipate that this interaction between an RTK and a component of NFÎºB signaling will not be limited to FGFR4 alone .
    OUTPUT:
