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: Gliomas display anoikis resistance , enhanced invasion in to the adjacent brain parenchyma and eventually recur despite using the standard therapies . Our studies on increased anoikis sensitization in matrix metalloproteinase-2 ( MMP-2)-knockdown 4910 and 5310 human glioma xenograft cells were interestingly correlated with p21-activated kinase 4 ( PAK4 ) inhibition , prompting us to further investigate the role of PAK4 in glioma . Here , we report the PAK4 upregulation in positive correlation with increasing glioma pathological grades . The siRNA-mediated PAK4 knockdown elevated anoikis , and inhibited invasion and migration by downregulating MMP-2 , Î±vÎ²3-integrin and phospho-epidermal growth factor receptor ( phospho-EGFR ) . The cDNA-PCR arrays revealed a transcriptional suppression of essential proteins involved in cell proliferation and adhesion in PAK4-knockdown cells . Most importantly , glutathione S-transferase pull-down assays demonstrated the MMP-2 as a new PAK4-interacting protein which binds to PAK4 kinase domain . Individual EGFR/ErbB2 inhibitor and Î±vÎ²3 antibody treatments in PAK4si-treated cells indicated the regulation of Î±vÎ²3/EGFR survival signaling by PAK4 . Overexpression of PAK4 significantly reversed the MMP2si-induced cell death in both cell lines . Codepletion of PAK4 and MMP-2 resulted in robust anoikis-mediated cell death , and severely inhibited invasive and migratory properties in these cells . PAK4si inhibited in vivo tumor growth in nude mice by inhibiting MMP-2 , Î²3-integrin and phospho-EGFR levels in tumors . Our findings indicate a physical association between PAK4 and MMP-2 , and suggest the future therapeutic potential of PAK4/MMP-2 dual targeting in glioma treatment .
    OUTPUT:

agent
activating invasion and metastasis;sustaining proliferative signaling;resisting cell death
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: Gliomas display anoikis resistance , enhanced invasion in to the adjacent brain parenchyma and eventually recur despite using the standard therapies . Our studies on increased anoikis sensitization in matrix metalloproteinase-2 ( MMP-2)-knockdown 4910 and 5310 human glioma xenograft cells were interestingly correlated with p21-activated kinase 4 ( PAK4 ) inhibition , prompting us to further investigate the role of PAK4 in glioma . Here , we report the PAK4 upregulation in positive correlation with increasing glioma pathological grades . The siRNA-mediated PAK4 knockdown elevated anoikis , and inhibited invasion and migration by downregulating MMP-2 , Î±vÎ²3-integrin and phospho-epidermal growth factor receptor ( phospho-EGFR ) . The cDNA-PCR arrays revealed a transcriptional suppression of essential proteins involved in cell proliferation and adhesion in PAK4-knockdown cells . Most importantly , glutathione S-transferase pull-down assays demonstrated the MMP-2 as a new PAK4-interacting protein which binds to PAK4 kinase domain . Individual EGFR/ErbB2 inhibitor and Î±vÎ²3 antibody treatments in PAK4si-treated cells indicated the regulation of Î±vÎ²3/EGFR survival signaling by PAK4 . Overexpression of PAK4 significantly reversed the MMP2si-induced cell death in both cell lines . Codepletion of PAK4 and MMP-2 resulted in robust anoikis-mediated cell death , and severely inhibited invasive and migratory properties in these cells . PAK4si inhibited in vivo tumor growth in nude mice by inhibiting MMP-2 , Î²3-integrin and phospho-EGFR levels in tumors . Our findings indicate a physical association between PAK4 and MMP-2 , and suggest the future therapeutic potential of PAK4/MMP-2 dual targeting in glioma treatment .
    OUTPUT:
