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10.18632/oncotarget.12781 http://scihub22266oqcxt.onion/10.18632/oncotarget.12781 C5363568!5363568!27780915     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=27780915&cmd=llinks): Failed to open stream: HTTP request failed! 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Efficacy of glycogen synthase kinase-3? targeting against osteosarcoma via activation of ?-catenin |pdf=|usr=}}{{27780915}} gab.com Text Efficacy of glycogen synthase kinase-3 targeting against osteosarcoma via activation of -catenin JO: Oncotarget http://www.kidney.de/pget.php?&tw=1&pmid=27780915 #FOAvip Development of innovative more effective therapy is required for refractory osteosarcoma patients. We previously established that glycogen synthase kinase-3? (GSK- 3?) is a therapeutic target in various cancer types. In the present study, we explored the therapeutic efficacy of GSK-3? inhibition against osteosarcoma and the underlying molecular mechanisms in an orthotopic mouse model. Expression and phosphorylation of GSK-3? in osteosarcoma and normal osteoblast cell lines was examined, together with efficacy of GSK-3? inhibition on cell survival, proliferation and apoptosis and on the growth of orthotopically-transplanted human osteosarcoma in nude mice. We also investigated changes in expression, phosphorylation and co-transcriptional activity of ?-catenin in osteosarcoma cells following GSK-3? inhibition. Expression of the active form of GSK- 3? (tyrosine 216-phosphorylated) was higher in osteosarcoma than osteoblast cells. Inhibition of GSK-3? activity by pharmacological inhibitors or of its expression by RNA interference suppressed proliferation of osteosarcoma cells and induced apoptosis. Treatment with GSK-3?-specific inhibitors attenuated the growth of orthotopic osteosaroma in mice. Inhibition of GSK-3? reduced phosphorylation at GSK- 3?-phospho-acceptor sites in ?-catenin and increased ?-catenin expression, nuclear localization and co-transcriptional activity. These results suggest the efficacy of GSK-3? inhibitors is associated with activation of ?-catenin, a putative tumor suppressor in bone and soft tissue sarcoma and an important component of osteogenesis. Our study thereby demonstrates a critical role for GSK-3? in sustaining survival and proliferation of osteosarcoma cells, and identifies this kinase as a potential therapeutic target against osteosarcoma. Twit Text FOAVip Efficacy of glycogen synthase kinase-3 targeting against osteosarcoma via activation of -catenin ????Oncotarget http://www.kidney.de/pget.php?&tw=1&pmid=27780915 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=27780915 #FOAvip English Wikipedia <ref>{{Cite pmid|27780915}}</ref> Efficacy of glycogen synthase kinase-3? targeting against osteosarcoma via activation of ?-catenin #MMPMID27780915 Shimozaki S; Yamamoto N; Domoto T; Nishida H; Hayashi K; Kimura H; Takeuchi A; Miwa S; Igarashi K; Kato T; Aoki Y; Higuchi T; Hirose M; Hoffman RM; Minamoto T; Tsuchiya H Oncotarget 2016[Nov]; 7 (47): 77038-51 PMID27780915show ga Development of innovative more effective therapy is required for refractory osteosarcoma patients. We previously established that glycogen synthase kinase-3? (GSK- 3?) is a therapeutic target in various cancer types. In the present study, we explored the therapeutic efficacy of GSK-3? inhibition against osteosarcoma and the underlying molecular mechanisms in an orthotopic mouse model. Expression and phosphorylation of GSK-3? in osteosarcoma and normal osteoblast cell lines was examined, together with efficacy of GSK-3? inhibition on cell survival, proliferation and apoptosis and on the growth of orthotopically-transplanted human osteosarcoma in nude mice. We also investigated changes in expression, phosphorylation and co-transcriptional activity of ?-catenin in osteosarcoma cells following GSK-3? inhibition. Expression of the active form of GSK- 3? (tyrosine 216-phosphorylated) was higher in osteosarcoma than osteoblast cells. Inhibition of GSK-3? activity by pharmacological inhibitors or of its expression by RNA interference suppressed proliferation of osteosarcoma cells and induced apoptosis. Treatment with GSK-3?-specific inhibitors attenuated the growth of orthotopic osteosaroma in mice. Inhibition of GSK-3? reduced phosphorylation at GSK- 3?-phospho-acceptor sites in ?-catenin and increased ?-catenin expression, nuclear localization and co-transcriptional activity. These results suggest the efficacy of GSK-3? inhibitors is associated with activation of ?-catenin, a putative tumor suppressor in bone and soft tissue sarcoma and an important component of osteogenesis. Our study thereby demonstrates a critical role for GSK-3? in sustaining survival and proliferation of osteosarcoma cells, and identifies this kinase as a potential therapeutic target against osteosarcoma. äEfficacy of glycogen synthase kinase-3? targeting against osteosarcoma(epmc).pdf DeepDyve Pubget Overpricing