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GPR177 promotes gastric cancer proliferation by suppressing endoplasmic reticulum stress‐induced cell death

 Jaesung Seo  ;  Seung‐H. Lee  ;  Soo‐Y. Park  ;  Mi‐H. Jeong  ;  Soo Y. Lee  ;  Mi‐J. Kim  ;  Jung‐Y. Yoo  ;  Subhin Jang  ;  Kyung‐C. Choi  ;  Ho-G. Yoon 
 Journal of Cellular Biochemistry, Vol.120(2) : 2535-2539, 2019 
Journal Title
 Journal of Cellular Biochemistry 
Issue Date
WLS/GPR177 ; apoptosis ; endoplasmic reticulum (ER) ; tunicamycin ; unfolded protein response
Gastric cancer is the fourth most common cancer worldwide. Despite the high incidence of gastric cancer, efficient chemotherapy treatments still need to be developed. In this study, we examined the anticancer effects of endoplasmic reticulum (ER) stress inducer tunicamycin in gastric cancer. Previously, we found that overexpression of WLS1/GPR177 correlated with poor prognosis in patients with gastric cancer. Furthermore, tunicamycin treatment downregulated GPR177 expression in a dose-dependent manner. GPR177 transports WNT ligand from ER to the plasma membrane, mediating its secretion to the extracellular matrix. In gastric cancer cells, GPR177 preferentially localizes to the ER. Small interfering RNA-mediated knockdown of GPR177 leads to sensitization to ER stress and induces apoptosis of cancer cells along with tunicamycin treatment. GPR177 suppression promoted the ER stress-mediated proapoptotic pathway, such as PERK-CHOP cascade. Furthermore, fluorouracil treatment combined with tunicamycin dramatically reduced cancer cell proliferation. Efficacy of tunicamycin chemotherapy treatments depended on GPR177 expression in gastric cancer cell lines. Together, our results indicate that ER stress can potentiate anticancer effects and suggest GPR177 as a potential gastric cancer therapeutic target.
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1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Others (기타) > 1. Journal Papers
Yonsei Authors
김미정(Kim, Mi Jeong) ORCID logo https://orcid.org/0000-0002-0758-7145
박수연(Park, Soo Yeon) ORCID logo https://orcid.org/0000-0003-3743-9554
유정윤(Yoo, Jung Yoon) ORCID logo https://orcid.org/0000-0001-9366-3863
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
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