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10.1158/1541-7786.MCR-15-0204 http://scihub22266oqcxt.onion/10.1158/1541-7786.MCR-15-0204 C4644680!4644680!26224368     free     free     free Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Mol+Cancer+Res 2015 ; 13 (11): 1509-19 Nephropedia Template TP {{tp|p=26224368|t=2015. Calcipotriol Targets LRP6 to Inhibit Wnt Signaling in Pancreatic Cancer |pdf=|usr=}}{{26224368}} gab.com Text Calcipotriol Targets LRP6 to Inhibit Wnt Signaling in Pancreatic Cancer JO: Mol Cancer Res http://www.kidney.de/pget.php?&tw=1&pmid=26224368 #FOAvip Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy in need of more effective treatment approaches. One potential therapeutic target is Wnt/?-catenin signaling, which plays important roles in PDAC tumor initiation and progression. Among Wnt inhibitors with suitable in vivo biological activity is vitamin D, which is known to antagonize Wnt/?-catenin signaling in colorectal cancer and have anti-tumor activity in PDAC. For this study the relationship between vitamin D signaling, Wnt/?-catenin activity and tumor cell growth in PDAC was investigated through the use of calcipotriol, a potent non-hypercalcemic vitamin D analog. PDAC tumor cell growth inhibition by calcipotriol was positively correlated with vitamin D receptor (VDR) expression and Wnt/?-catenin activity. Furthermore, vitamin D and Wnt signaling activity were found to be reciprocally linked through feedback regulation. Calcipotriol inhibited autocrine Wnt/?-catenin signaling in PDAC cell lines in parallel with decreased protein levels of the low density lipoprotein receptor-related protein 6 (LRP6), a requisite co-receptor for ligand-dependent canonical Wnt signaling. Decrease in LRP6 protein seen with calcipotriol was mediated through a novel mechanism involving transcriptional upregulation of low-density lipoprotein receptor adaptor protein 1 (LDLRAP1). Finally, changes in LRP6 or LDLRAP1 expression directly altered Wnt reporter activity, supporting their roles as regulators of ligand-dependent Wnt/?-catenin signaling.Implications: This study provides a novel biochemical target through which vitamin D signaling exerts inhibitory effects on Wnt/?-catenin signaling, as well as potential biomarkers for predicting and following tumor response to vitamin D-based therapy. Twit Text FOAVip Calcipotriol Targets LRP6 to Inhibit Wnt Signaling in Pancreatic Cancer ????Mol Cancer Res http://www.kidney.de/pget.php?&tw=1&pmid=26224368 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=26224368 #FOAvip English Wikipedia <ref>{{Cite pmid|26224368}}</ref> Calcipotriol Targets LRP6 to Inhibit Wnt Signaling in Pancreatic Cancer #MMPMID26224368 Arensman MD; Nguyen P; Kershaw KM; Lay AR; Ostertag-Hill CA; Sherman MH; Downes M; Liddle C; Evans RM; Dawson DW Mol Cancer Res 2015[Nov]; 13 (11): 1509-19 PMID26224368show ga Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy in need of more effective treatment approaches. One potential therapeutic target is Wnt/?-catenin signaling, which plays important roles in PDAC tumor initiation and progression. Among Wnt inhibitors with suitable in vivo biological activity is vitamin D, which is known to antagonize Wnt/?-catenin signaling in colorectal cancer and have anti-tumor activity in PDAC. For this study the relationship between vitamin D signaling, Wnt/?-catenin activity and tumor cell growth in PDAC was investigated through the use of calcipotriol, a potent non-hypercalcemic vitamin D analog. PDAC tumor cell growth inhibition by calcipotriol was positively correlated with vitamin D receptor (VDR) expression and Wnt/?-catenin activity. Furthermore, vitamin D and Wnt signaling activity were found to be reciprocally linked through feedback regulation. Calcipotriol inhibited autocrine Wnt/?-catenin signaling in PDAC cell lines in parallel with decreased protein levels of the low density lipoprotein receptor-related protein 6 (LRP6), a requisite co-receptor for ligand-dependent canonical Wnt signaling. Decrease in LRP6 protein seen with calcipotriol was mediated through a novel mechanism involving transcriptional upregulation of low-density lipoprotein receptor adaptor protein 1 (LDLRAP1). Finally, changes in LRP6 or LDLRAP1 expression directly altered Wnt reporter activity, supporting their roles as regulators of ligand-dependent Wnt/?-catenin signaling.Implications: This study provides a novel biochemical target through which vitamin D signaling exerts inhibitory effects on Wnt/?-catenin signaling, as well as potential biomarkers for predicting and following tumor response to vitamin D-based therapy. äCalcipotriol Targets LRP6 to Inhibit Wnt Signaling in Pancreatic Cance(epmc).pdf DeepDyve Pubget Overpricing