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10.1016/j.neo.2015.06.004 http://scihub22266oqcxt.onion/10.1016/j.neo.2015.06.004 C4547409!4547409 !26297431     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26297431 &cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 219.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 253.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 253.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 253.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 253.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 253.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 253.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 253.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 253.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 253.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 253.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 286.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 286.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 286.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 286.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 286.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 286.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 320.4 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 320.4 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\26297431 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Neoplasia 2015 ; 17 (7 ): 525-37 Nephropedia Template TP {{tp|p=26297431 |t=2015. Kaempferol Suppresses Transforming Growth Factor-?1-Induced Epithelial-to-Mesenchymal Transition and Migration of A549 Lung Cancer Cells by Inhibiting Akt1-Mediated Phosphorylation of Smad3 at Threonine-179 |pdf=|usr=}}{{26297431 }} gab.com Text Kaempferol Suppresses Transforming Growth Factor- 1-Induced Epithelial-to-Mesenchymal Transition and Migration of A549 Lung Cancer Cells by Inhibiting Akt1-Mediated Phosphorylation of Smad3 at Threonine-179 JO: Neoplasia http://www.kidney.de/pget.php?&tw=1&pmid=26297431 #FOAvip Kaempferol, a natural dietary flavonoid, is well known to possess chemopreventive and therapeutic anticancer efficacy; however, its antimetastatic effects have not been mechanistically studied so far in any cancer model. This study was aimed to investigate the inhibitory effect and accompanying mechanisms of kaempferol on epithelial-to-mesenchymal transition (EMT) and cell migration induced by transforming growth factor-?1 (TGF-?1). In human A549 non-small lung cancer cells, kaempferol strongly blocked the enhancement of cell migration by TGF-?1-induced EMT through recovering the loss of E-cadherin and suppressing the induction of mesenchymal markers as well as the upregulation of TGF-?1-mediated matrix metalloproteinase-2 activity. Interestingly, kaempferol reversed TGF-?1-mediated Snail induction and E-cadherin repression by weakening Smad3 binding to the Snail promoter without affecting its C-terminus phosphorylation, complex formation with Smad4, and nuclear translocation under TGF-?1 stimulation. Mechanism study revealed that the phosphorylation of Smad3 linker region induced by TGF-?1 was required for the induction of EMT and cell migration, and selective downregulation of the phosphorylation of Smad3 at Thr179 residue (not Ser204, Ser208, and Ser213) in the linker region was responsible for the inhibition by kaempferol of TGF-?1-induced EMT and cell migration. Furthermore, Akt1 was required for TGF-?1-mediated induction of EMT and cell migration and directly phosphorylated Smad3 at Thr179, and kaempferol completely abolished TGF-?1-induced Akt1 phosphorylation. In summary, kaempferol blocks TGF-?1-induced EMT and migration of lung cancer cells by inhibiting Akt1-mediated phosphorylation of Smad3 at Thr179 residue, providing the first evidence of a molecular mechanism for the anticancer effect of kaempferol. Twit Text FOAVip Kaempferol Suppresses Transforming Growth Factor- 1-Induced Epithelial-to-Mesenchymal Transition and Migration of A549 Lung Cancer Cells by Inhibiting Akt1-Mediated Phosphorylation of Smad3 at Threonine-179 ????Neoplasia http://www.kidney.de/pget.php?&tw=1&pmid=26297431 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26297431 #FOAvip English Wikipedia <ref>{{Cite pmid|26297431 }}</ref> Kaempferol Suppresses Transforming Growth Factor-?1-Induced Epithelial-to-Mesenchymal Transition and Migration of A549 Lung Cancer Cells by Inhibiting Akt1-Mediated Phosphorylation of Smad3 at Threonine-179 #MMPMID26297431 Jo E ; Park SJ ; Choi YS ; Jeon WK ; Kim BC Neoplasia 2015[Jul]; 17 (7 ): 525-37 PMID26297431 show ga Kaempferol, a natural dietary flavonoid, is well known to possess chemopreventive and therapeutic anticancer efficacy; however, its antimetastatic effects have not been mechanistically studied so far in any cancer model. This study was aimed to investigate the inhibitory effect and accompanying mechanisms of kaempferol on epithelial-to-mesenchymal transition (EMT) and cell migration induced by transforming growth factor-?1 (TGF-?1). In human A549 non-small lung cancer cells, kaempferol strongly blocked the enhancement of cell migration by TGF-?1-induced EMT through recovering the loss of E-cadherin and suppressing the induction of mesenchymal markers as well as the upregulation of TGF-?1-mediated matrix metalloproteinase-2 activity. Interestingly, kaempferol reversed TGF-?1-mediated Snail induction and E-cadherin repression by weakening Smad3 binding to the Snail promoter without affecting its C-terminus phosphorylation, complex formation with Smad4, and nuclear translocation under TGF-?1 stimulation. Mechanism study revealed that the phosphorylation of Smad3 linker region induced by TGF-?1 was required for the induction of EMT and cell migration, and selective downregulation of the phosphorylation of Smad3 at Thr179 residue (not Ser204, Ser208, and Ser213) in the linker region was responsible for the inhibition by kaempferol of TGF-?1-induced EMT and cell migration. Furthermore, Akt1 was required for TGF-?1-mediated induction of EMT and cell migration and directly phosphorylated Smad3 at Thr179, and kaempferol completely abolished TGF-?1-induced Akt1 phosphorylation. In summary, kaempferol blocks TGF-?1-induced EMT and migration of lung cancer cells by inhibiting Akt1-mediated phosphorylation of Smad3 at Thr179 residue, providing the first evidence of a molecular mechanism for the anticancer effect of kaempferol. |Active Transport, Cell Nucleus/drug effects [MESH] |Antineoplastic Agents/pharmacology [MESH] |Cadherins/metabolism [MESH] |Carcinoma, Non-Small-Cell Lung/pathology [MESH] |Cell Line, Tumor [MESH] |Cell Movement/*drug effects [MESH] |DNA-Binding Proteins/antagonists & inhibitors [MESH] |Epithelial-Mesenchymal Transition/*drug effects [MESH] |Humans [MESH] |Kaempferols/*pharmacology [MESH] |Lung Neoplasms/pathology [MESH] |Matrix Metalloproteinase 2/metabolism [MESH] |Neoplasm Metastasis/prevention & control [MESH] |Phosphorylation [MESH] |Promoter Regions, Genetic/genetics [MESH] |Protein Transport/drug effects [MESH] |Proto-Oncogene Proteins c-akt/*antagonists & inhibitors/metabolism [MESH] |Smad3 Protein/*metabolism [MESH] |Smad4 Protein/metabolism [MESH] |Snail Family Transcription Factors [MESH] |Transcription Factors/genetics/metabolism [MESH]Kaempferol Suppresses Transforming Growth Factor-?1-Induced Epitheli(epmc).pdf DeepDyve Pubget Overpricing