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Inhibition of Wntless/GPR177 suppresses gastric tumorigenesis

 Jaesung Seo  ;  Hyun Jung Kee  ;  Hye Ji Choi  ;  Jae Eun Lee  ;  Soo-Yeon Park  ;  Seung-Hyun Lee  ;  Mi-Hyeon Jeong  ;  Garam Guk  ;  SooYeon Lee  ;  Kyung-Chul Choi  ;  Yoon Young Choi  ;  Hyunki Kim  ;  Sung Hoon Noh  ;  Ho-Geun Yoon  ;  Jae-Ho Cheong 
 BMB Reports, Vol.51(5) : 255-260, 2018 
Journal Title
 BMB Reports 
Issue Date
Wntless/GPR177 functions as WNT ligand carrier protein and activator of WNT/beta-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/beta-catenin signaling. Finally, targeting and inhibition of GPR177 with antibody suppressed tumorigenesis in PDX model. Together, these results suggest GPR177 as a novel candidate for prognostic marker as well as a promising target for treatment of GC patients. [BMB Reports 2018; 51(5): 255-260].
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1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실)
Yonsei Authors
기현정(Kee, Hyun Jung) ORCID logo https://orcid.org/0000-0003-4350-1852
김미정(Kim, Mi Jeong) ORCID logo https://orcid.org/0000-0002-0758-7145
김현기(Kim, Hyunki) ORCID logo https://orcid.org/0000-0003-2292-5584
노성훈(Noh, Sung Hoon) ORCID logo https://orcid.org/0000-0003-4386-6886
박수연(Park, Soo Yeon) ORCID logo https://orcid.org/0000-0003-3743-9554
윤호근(Yoon, Ho Geun) ORCID logo https://orcid.org/0000-0003-2718-3372
이승현(Lee, Seung Hyun) ORCID logo https://orcid.org/0000-0001-7549-9430
정재호(Cheong, Jae Ho)
최윤영(Choi, Yoon Young) ORCID logo https://orcid.org/0000-0002-2179-7851
최혜지(Choi, Hye Ji)
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