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10.1038/s41421-018-0033-2 http://scihub22266oqcxt.onion/10.1038/s41421-018-0033-2 C6028397!6028397 !29977599     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 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 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\29977599 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Cell+Discov 2018 ; 4 (ä): 37 Nephropedia Template TP {{tp|p=29977599 |t=2018. Cancer cell specific inhibition of Wnt/?-catenin signaling by forced intracellular acidification |pdf=|usr=}}{{29977599 }} gab.com Text Cancer cell specific inhibition of Wnt/ -catenin signaling by forced intracellular acidification JO: Cell Discov http://www.kidney.de/pget.php?&tw=1&pmid=29977599 #FOAvip Use of the diabetes type II drug Metformin is associated with a moderately lowered risk of cancer incidence in numerous tumor entities. Studying the molecular changes associated with the tumor-suppressive action of Metformin we found that the oncogene SOX4, which is upregulated in solid tumors and associated with poor prognosis, was induced by Wnt/?-catenin signaling and blocked by Metformin. Wnt signaling inhibition by Metformin was surprisingly specific for cancer cells. Unraveling the underlying specificity, we identified Metformin and other Mitochondrial Complex I (MCI) inhibitors as inducers of intracellular acidification in cancer cells. We demonstrated that acidification triggers the unfolded protein response to induce the global transcriptional repressor DDIT3, known to block Wnt signaling. Moreover, our results suggest that intracellular acidification universally inhibits Wnt signaling. Based on these findings, we combined MCI inhibitors with H(+) ionophores, to escalate cancer cells into intracellular hyper-acidification and ATP depletion. This treatment lowered intracellular pH both in vitro and in a mouse xenograft tumor model, depleted cellular ATP, blocked Wnt signaling, downregulated SOX4, and strongly decreased stemness and viability of cancer cells. Importantly, the inhibition of Wnt signaling occurred downstream of ?-catenin, encouraging applications in treatment of cancers caused by APC and ?-catenin mutations. Twit Text FOAVip Cancer cell specific inhibition of Wnt/ -catenin signaling by forced intracellular acidification ????Cell Discov http://www.kidney.de/pget.php?&tw=1&pmid=29977599 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29977599 #FOAvip English Wikipedia <ref>{{Cite pmid|29977599 }}</ref> Cancer cell specific inhibition of Wnt/?-catenin signaling by forced intracellular acidification #MMPMID29977599 Melnik S ; Dvornikov D ; Müller-Decker K ; Depner S ; Stannek P ; Meister M ; Warth A ; Thomas M ; Muley T ; Risch A ; Plass C ; Klingmüller U ; Niehrs C ; Glinka A Cell Discov 2018[]; 4 (ä): 37 PMID29977599 show ga Use of the diabetes type II drug Metformin is associated with a moderately lowered risk of cancer incidence in numerous tumor entities. Studying the molecular changes associated with the tumor-suppressive action of Metformin we found that the oncogene SOX4, which is upregulated in solid tumors and associated with poor prognosis, was induced by Wnt/?-catenin signaling and blocked by Metformin. Wnt signaling inhibition by Metformin was surprisingly specific for cancer cells. Unraveling the underlying specificity, we identified Metformin and other Mitochondrial Complex I (MCI) inhibitors as inducers of intracellular acidification in cancer cells. We demonstrated that acidification triggers the unfolded protein response to induce the global transcriptional repressor DDIT3, known to block Wnt signaling. Moreover, our results suggest that intracellular acidification universally inhibits Wnt signaling. Based on these findings, we combined MCI inhibitors with H(+) ionophores, to escalate cancer cells into intracellular hyper-acidification and ATP depletion. This treatment lowered intracellular pH both in vitro and in a mouse xenograft tumor model, depleted cellular ATP, blocked Wnt signaling, downregulated SOX4, and strongly decreased stemness and viability of cancer cells. Importantly, the inhibition of Wnt signaling occurred downstream of ?-catenin, encouraging applications in treatment of cancers caused by APC and ?-catenin mutations. äCancer cell specific inhibition of Wnt/?-catenin signaling by forced (epmc).pdf DeepDyve Pubget Overpricing