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: Hepatocellular carcinoma ( HCC ) is the most prevalent liver tumor and a deadly disease with limited therapeutic options . Dysregulation of cell signaling pathways is a common denominator in tumorigenesis , including hepatocarcinogenesis . The epidermal growth factor receptor ( EGFR ) signaling system is commonly activated in HCC , and is currently being evaluated as a therapeutic target in combination therapies . We and others have identified a central role for the EGFR ligand amphiregulin ( AR ) in the proliferation , survival and drug resistance of HCC cells . AR expression is frequently up-regulated in HCC tissues and cells through mechanisms not completely known . Here we identify the Î²-catenin signaling pathway as a novel mechanism leading to transcriptional activation of the AR gene in human HCC cells . Activation of Î²-catenin signaling , or expression of the T41A Î²-catenin active mutant , led to the induction of AR expression involving three specific Î²-catenin-Tcf responsive elements in its proximal promoter . We demonstrate that HCC cells expressing the T41A Î²-catenin active mutant show enhanced proliferation that is dependent in part on AR expression and EGFR signaling . We also demonstrate here a novel cross-talk of the EGFR system with fibroblast growth factor 19 ( FGF19 ) . FGF19 is a recently identified driver gene in hepatocarcinogenesis and an activator of Î²-catenin signaling in HCC and colon cancer cells . We show that FGF19 induced AR gene expression through the Î²-catenin pathway in human HCC cells . Importantly , AR up-regulation and EGFR signaling participated in the induction of cyclin D1 and cell proliferation elicited by FGF19 . Finally , we demonstrate a positive correlation between FGF19 and AR expression in human HCC tissues , therefore supporting in clinical samples our experimental observations . These findings identify the AR/EGFR system as a key mediator of FGF19 responses in HCC cells involving Î²-catenin signaling , and suggest that combined targeting of FGF19 and AR/EGFR may enhance therapeutic efficacy .
    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: Hepatocellular carcinoma ( HCC ) is the most prevalent liver tumor and a deadly disease with limited therapeutic options . Dysregulation of cell signaling pathways is a common denominator in tumorigenesis , including hepatocarcinogenesis . The epidermal growth factor receptor ( EGFR ) signaling system is commonly activated in HCC , and is currently being evaluated as a therapeutic target in combination therapies . We and others have identified a central role for the EGFR ligand amphiregulin ( AR ) in the proliferation , survival and drug resistance of HCC cells . AR expression is frequently up-regulated in HCC tissues and cells through mechanisms not completely known . Here we identify the Î²-catenin signaling pathway as a novel mechanism leading to transcriptional activation of the AR gene in human HCC cells . Activation of Î²-catenin signaling , or expression of the T41A Î²-catenin active mutant , led to the induction of AR expression involving three specific Î²-catenin-Tcf responsive elements in its proximal promoter . We demonstrate that HCC cells expressing the T41A Î²-catenin active mutant show enhanced proliferation that is dependent in part on AR expression and EGFR signaling . We also demonstrate here a novel cross-talk of the EGFR system with fibroblast growth factor 19 ( FGF19 ) . FGF19 is a recently identified driver gene in hepatocarcinogenesis and an activator of Î²-catenin signaling in HCC and colon cancer cells . We show that FGF19 induced AR gene expression through the Î²-catenin pathway in human HCC cells . Importantly , AR up-regulation and EGFR signaling participated in the induction of cyclin D1 and cell proliferation elicited by FGF19 . Finally , we demonstrate a positive correlation between FGF19 and AR expression in human HCC tissues , therefore supporting in clinical samples our experimental observations . These findings identify the AR/EGFR system as a key mediator of FGF19 responses in HCC cells involving Î²-catenin signaling , and suggest that combined targeting of FGF19 and AR/EGFR may enhance therapeutic efficacy .
    OUTPUT:
