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

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

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. Previou...

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Published in:Journal of cellular biochemistry Vol. 120; no. 2; pp. 2532 - 2539
Main Authors: Seo, Jaesung, Lee, Seung‐H., Park, Soo‐Y., Jeong, Mi‐H., Lee, Soo Y., Kim, Mi‐J., Yoo, Jung‐Y., Jang, Subhin, Choi, Kyung‐C., Yoon,  Ho‐G.
Format: Journal Article
Language:English
Published: United States Wiley Subscription Services, Inc 01-02-2019
Subjects:
5-Fluorouracil
Anticancer properties
Apoptosis
Cancer
Cancer therapies
Cell death
Cell proliferation
Chemotherapy
Endoplasmic reticulum
endoplasmic reticulum (ER)
Extracellular matrix
Gastric cancer
Ribonucleic acid
RNA
Secretion
siRNA
Stress
Therapeutic applications
Tumor cell lines
Tunicamycin
unfolded protein response
WLS/GPR177
Wnt protein
unfolded protein response
apoptosis
WLS/GPR177
endoplasmic reticulum (ER)
tunicamycin
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Summary: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. GPR177 translocates in the golgi upon wnt signal‐ gpr177 suppression promoted the endoplasmic reticulum stress‐mediated proapoptotic pathway‐ tunicamycin and siRNA‐mediated GPR177 knockdown additively reduce gastric cancer cell viability.
Bibliography:Jaesung Seo and Seung‐H. Lee contributed equally to this study.
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ISSN:0730-2312
1097-4644
DOI:10.1002/jcb.27545