Inhibition of Wntless/GPR177 suppresses gastric tumorigenesis.

Inhibition of Wntless/GPR177 suppresses gastric tumorigenesis. BMB Rep. 2018 Mar 20;: Authors: Seo J, Kee HJ, Choi HJ, Lee JE, Park SY, Lee SH, Jeong MH, Guk G, Lee S, Choi KC, Choi YY, Kim H, Noh SH, Yoon HG, Cheong JH Abstract Wntless/GPR177 functions as WNT ligand carrier protein and activator of WNT/β-catenin signaling, however, its molecular role in gastric cancer (GC) has remained elusive. We investigated the role of GPR177 in gastric tumorigenesis and provided the therapeutic potential of a clinical development of anti-GPR177 monoclonal antibodies. GPR177 mRNA expression was assessed in GC transcriptome data sets (GSE15459, n=184; GSE66229, n=300); protein expression was assessed in independent patient tumor tissues (Yonsei TMA, n=909). GPR177 expression were associated with unfavorable prognosis [log-rank test, GSE15459 (p=0.00736), GSE66229 (p=0.0142), and Yonsei TMA (p=0.0334)] and identified as an independent risk predictor of clinical outcomes: GSE15459 [hazard ratio (HR) 1.731 (95% confidence interval; CI; 1.103-2.715), p=0.017], GSE66229 [HR 1.54 (95% CI, 1.10-2.151), p=0.011], and Yonsei TMA [HR 1.254 (95% CI, 1.049-1.500), p=0.013]. Either antibody treatment or GPR177 knockdown suppressed proliferation of GC cells and sensitized cells to apoptosis. And also inhibition of GPR177 suppresses in vitro and in vivo tumorogenesis in GC cells and inhibits WNT/β-catenin signaling. Finally, targeting and inhibition of GPR177 ...
Source: BMB Reports - Category: Biochemistry Authors: Tags: BMB Rep Source Type: research