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10.18632/oncotarget.18963 http://scihub22266oqcxt.onion/10.18632/oncotarget.18963 C5589626!5589626 !28903387     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\28903387 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Oncotarget 2017 ; 8 (33 ): 54858-54872 Nephropedia Template TP {{tp|p=28903387 |t=2017. Hyperactivated mTORC1 downregulation of FOXO3a/PDGFR?/AKT cascade restrains tuberous sclerosis complex-associated tumor development |pdf=|usr=}}{{28903387 }} gab.com Text Hyperactivated mTORC1 downregulation of FOXO3a/PDGFR /AKT cascade restrains tuberous sclerosis complex-associated tumor development JO: Oncotarget http://www.kidney.de/pget.php?&tw=1&pmid=28903387 #FOAvip Hyperactivation of mammalian target of rapamycin complex 1 (mTORC1), caused by loss-of-function mutations in either the TSC1 or TSC2 gene, leads to the development of tuberous sclerosis complex (TSC), a benign tumor syndrome with multiple affected organs. mTORC1-mediated inhibition of AKT constrains the tumor progression of TSC, but the exact mechanisms remain unclear. Herein we showed that loss of TSC1 or TSC2 downregulation of platelet-derived growth factor receptor ? (PDGFR?) expression was mediated by mTORC1. Moreover, mTORC1 inhibited PDGFR? expression via suppression of forkhead box O3a (FOXO3a)-mediated PDGFR? gene transcription. In addition, ectopic expression of PDGFR? promoted AKT activation and enhanced proliferation and tumorigenic capacity of Tsc1- or Tsc2-null mouse embryonic fibroblasts (MEFs), and vice versa. Most importantly, rapamycin in combination with AG1295, a PDGFR inhibitor, significantly inhibited growth of TSC1/TSC2 complex-deficient cells in vitro and in vivo. Therefore, downregulated FOXO3a/PDGFR?/AKT pathway exerts a protective effect against hyperactivated mTORC1-induced tumorigenesis caused by loss of TSC1/TSC2 complex, and the combination of rapamycin and AG1295 may be a new effective strategy for TSC-associated tumors treatment. Twit Text FOAVip Hyperactivated mTORC1 downregulation of FOXO3a/PDGFR /AKT cascade restrains tuberous sclerosis complex-associated tumor development ????Oncotarget http://www.kidney.de/pget.php?&tw=1&pmid=28903387 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28903387 #FOAvip English Wikipedia <ref>{{Cite pmid|28903387 }}</ref> Hyperactivated mTORC1 downregulation of FOXO3a/PDGFR?/AKT cascade restrains tuberous sclerosis complex-associated tumor development #MMPMID28903387 Wang L ; Ni Z ; Liu Y ; Ji S ; Jin F ; Jiang K ; Ma J ; Ren C ; Zhang H ; Hu Z ; Zha X Oncotarget 2017[Aug]; 8 (33 ): 54858-54872 PMID28903387 show ga Hyperactivation of mammalian target of rapamycin complex 1 (mTORC1), caused by loss-of-function mutations in either the TSC1 or TSC2 gene, leads to the development of tuberous sclerosis complex (TSC), a benign tumor syndrome with multiple affected organs. mTORC1-mediated inhibition of AKT constrains the tumor progression of TSC, but the exact mechanisms remain unclear. Herein we showed that loss of TSC1 or TSC2 downregulation of platelet-derived growth factor receptor ? (PDGFR?) expression was mediated by mTORC1. Moreover, mTORC1 inhibited PDGFR? expression via suppression of forkhead box O3a (FOXO3a)-mediated PDGFR? gene transcription. In addition, ectopic expression of PDGFR? promoted AKT activation and enhanced proliferation and tumorigenic capacity of Tsc1- or Tsc2-null mouse embryonic fibroblasts (MEFs), and vice versa. Most importantly, rapamycin in combination with AG1295, a PDGFR inhibitor, significantly inhibited growth of TSC1/TSC2 complex-deficient cells in vitro and in vivo. Therefore, downregulated FOXO3a/PDGFR?/AKT pathway exerts a protective effect against hyperactivated mTORC1-induced tumorigenesis caused by loss of TSC1/TSC2 complex, and the combination of rapamycin and AG1295 may be a new effective strategy for TSC-associated tumors treatment. äHyperactivated mTORC1 downregulation of FOXO3a/PDGFR?/AKT cascade rest(epmc).pdf DeepDyve Pubget Overpricing