@Article{096504016X14783691306605,
AUTHOR = {Xiaohe Guo, Lanfang Zhang, Yingying Fan, Dezhong Zhang, Lei Qin, Shuping Dong, Guangyan Li},
TITLE = {Oxysterol-Binding Protein-Related Protein 8 Inhibits Gastric Cancer  Growth Through Induction of ER Stress, Inhibition of Wnt  Signaling, and Activation of Apoptosis},
JOURNAL = {Oncology Research},
VOLUME = {25},
YEAR = {2017},
NUMBER = {5},
PAGES = {799--808},
URL = {http://www.techscience.com/or/v25n5/56862},
ISSN = {1555-3906},
ABSTRACT = {Gastric cancer (GC) is the third leading cause of cancer-related mortality worldwide. Oxysterol-binding proteinrelated protein 8 (ORP8) functions as a sterol sensor that regulates a number of cellular functions. We showed 
that ORP8 expression was significantly lower in GC tissues and cells. Overexpression of ORP8 significantly 
inhibited GC cell proliferation in several GC cells. The formation of colonies in AGS cells was inhibited by the 
overexpression of ORP8. Moreover, overexpression of ORP8 significantly decreased implanted tumor growth 
in nude mice. Overexpression of ORP8 resulted in a significant increase in CHOP and GRP78 expression and 
the phosphorylation of PERK, indicating the occurrence of ER stress. Inhibition of ER stress by 4-PBA notably 
suppressed overexpression of ORP8-induced decrease of GC cell proliferation, formation of colonies, and 
implanted tumor growth. Overexpression of ORP8 resulted in a significant decrease in Wnt3a and β-catenin 
expression, and activation of Wnt signaling by HLY78 markedly blocked overexpression of ORP8-induced 
decrease in GC cell proliferation, formation of colonies, and implanted tumor growth. 4-PBA inhibited overexpression of ORP8-induced decrease in Wnt signaling. Furthermore, overexpression of ORP8 resulted in significant activation of mitochondrial apoptotic events and increase in apoptosis, which was inhibited by 4-PBA 
and HLY78. Induction of ER stress, inhibition of Wnt signaling, and apoptotic cell death were involved in 
ORP8-induced inhibition of GC cell proliferation. These findings indicate that downregulation of ORP8 plays 
a pivotal role in the progression of GC, and it may be a novel therapeutic target in the treatment of GC.},
DOI = {10.3727/096504016X14783691306605}
}