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10.1186/s13046-018-0801-8 http://scihub22266oqcxt.onion/10.1186/s13046-018-0801-8 C6020243!6020243!29940988     free     free     free Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       J+Exp+Clin+Cancer+Res 2018 ; 37 (ä): ä Nephropedia Template TP {{tp|p=29940988|t=2018. Prolonged inhibition of class I PI3K promotes liver cancer stem cell expansion by augmenting SGK3/GSK-3?/?-catenin signalling |pdf=|usr=}}{{29940988}} gab.com Text Prolonged inhibition of class I PI3K promotes liver cancer stem cell expansion by augmenting SGK3/GSK-3 / -catenin signalling JO: J Exp Clin Cancer Res http://www.kidney.de/pget.php?&tw=1&pmid=29940988 #FOAvip Background: Serum and glucocorticoid-regulated kinase 3 (SGK3) has been reported to play an important role in tumour progression, but its role in cancer stem cells (CSCs) remains obscure. The phosphoinositide 3-kinase (PI3K) pathway is considered a hallmark of cancer. Although many PI3K pathway-targeted therapies have been tested in oncology trials, the results are not satisfactory. Methods: We used spheroids cultured in serum-free culture medium and MicroBead isolation to obtain liver CSCs. Spheroid formation assay and flow cytometric analysis were performed to investigate liver CSC expansion. Real-time polymerase chain reaction (PCR), western blot and immunofluorescence were used to assess gene expression in cell lines. Results: We found that SGK3 is preferentially activated in liver CSCs. Upregulated SGK3 significantly increases the expansion of liver CSCs. Conversely, suppression of SGK3 in human hepatocarcinoma (HCC) cells had an opposite effect. Mechanistically, SGK3 promoted ?-catenin accumulation by suppressing GSK-3?-mediated ?-catenin degradation in liver CSCs, and then promoting the expansion of liver CSCs. Prolonged treatment of HCC cells with class I PI3K inhibitors leads to activation of SGK3 and expansion of liver CSCs. Inhibition of hVps34 can block SGK3 activity and suppress liver CSC expansion induced by PI3K inhibitors. More importantly, we also found that prolonged treatment of HCC cells with PI3K inhibitors stimulates the ?-catenin signalling pathway via activation of SGK3. Conclusions: Prolonged inhibition of class I PI3K promotes liver CSC expansion by augmenting SGK3-dependent ?-catenin stabilisation, and effective inhibition of SGK3 signalling may be useful in eliminating liver CSCs and in PI3K pathway-targeted cancer therapies. Electronic supplementary material: The online version of this article (10.1186/s13046-018-0801-8) contains supplementary material, which is available to authorized users. Twit Text FOAVip Prolonged inhibition of class I PI3K promotes liver cancer stem cell expansion by augmenting SGK3/GSK-3 / -catenin signalling ????J Exp Clin Cancer Res http://www.kidney.de/pget.php?&tw=1&pmid=29940988 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29940988 #FOAvip English Wikipedia <ref>{{Cite pmid|29940988}}</ref> Prolonged inhibition of class I PI3K promotes liver cancer stem cell expansion by augmenting SGK3/GSK-3?/?-catenin signalling #MMPMID29940988 Liu F; Wu X; Jiang X; Qian Y; Gao J J Exp Clin Cancer Res 2018[]; 37 (ä): ä PMID29940988show ga Background: Serum and glucocorticoid-regulated kinase 3 (SGK3) has been reported to play an important role in tumour progression, but its role in cancer stem cells (CSCs) remains obscure. The phosphoinositide 3-kinase (PI3K) pathway is considered a hallmark of cancer. Although many PI3K pathway-targeted therapies have been tested in oncology trials, the results are not satisfactory. Methods: We used spheroids cultured in serum-free culture medium and MicroBead isolation to obtain liver CSCs. Spheroid formation assay and flow cytometric analysis were performed to investigate liver CSC expansion. Real-time polymerase chain reaction (PCR), western blot and immunofluorescence were used to assess gene expression in cell lines. Results: We found that SGK3 is preferentially activated in liver CSCs. Upregulated SGK3 significantly increases the expansion of liver CSCs. Conversely, suppression of SGK3 in human hepatocarcinoma (HCC) cells had an opposite effect. Mechanistically, SGK3 promoted ?-catenin accumulation by suppressing GSK-3?-mediated ?-catenin degradation in liver CSCs, and then promoting the expansion of liver CSCs. Prolonged treatment of HCC cells with class I PI3K inhibitors leads to activation of SGK3 and expansion of liver CSCs. Inhibition of hVps34 can block SGK3 activity and suppress liver CSC expansion induced by PI3K inhibitors. More importantly, we also found that prolonged treatment of HCC cells with PI3K inhibitors stimulates the ?-catenin signalling pathway via activation of SGK3. Conclusions: Prolonged inhibition of class I PI3K promotes liver CSC expansion by augmenting SGK3-dependent ?-catenin stabilisation, and effective inhibition of SGK3 signalling may be useful in eliminating liver CSCs and in PI3K pathway-targeted cancer therapies. Electronic supplementary material: The online version of this article (10.1186/s13046-018-0801-8) contains supplementary material, which is available to authorized users. äProlonged inhibition of class I PI3K promotes liver cancer stem cell e(epmc).pdf DeepDyve Pubget Overpricing