title: ROR2 inhibits the proliferation of gastric carcinoma cells via activation of non-canonical Wnt signaling.
abstract: Gastric carcinoma is one of the most common human cancers and has a poor prognosis. Receptor tyrosine kinase-like orphan receptor 2 (ROR2), which is a non-canonical receptor of the Wnt signaling pathway, has been reported to be deregulated in numerous types of human cancers, including gastric carcinoma. However, the exact role of ROR2 in the regulation of the malignant phenotypes of gastric carcinoma, as well as the underlying molecular mechanism, remains largely unclear. The present study demonstrated that ROR2 was recurrently downregulated in gastric carcinoma tissues, as compared with their matched adjacent normal tissues. Furthermore, the expression levels of ROR2 were reduced in several common gastric carcinoma cell lines, as compared with normal gastric epithelial cells. Gastric carcinoma cells were transfected with ROR2 plasmids, and it was demonstrated that restoration of ROR2 expression significantly inhibited the proliferation and induced the apoptosis of gastric carcinoma cells by a Wnt5a-independent mechanism. In addition, it was observed that ROR2-overexpressing cells accumulated in the G0/G1 phase; thus suggesting that overexpression of ROR2 induced cell cycle arrest at the G0/G1 phase. An investigation of the underlying mechanism demonstrated that activation of the non-canonical Wnt signaling pathway inhibited canonical Wnt signal transduction, as demonstrated by the decreased level of β-catenin in nuclei, as well as the reduced expression levels of c-Myc. The results of the present study indicated a tumor suppressive role for ROR2 in gastric carcinoma growthin vitro, and suggested that ROR2 may be used as a molecular target for the treatment of gastric carcinoma.
authors.affiliation: Department of General Surgery, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China.
authors.forename: Likun
authors.initials: L
authors.lastname: Yan
authors.affiliation: Department of General Surgery, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China.
authors.forename: Qingguo
authors.initials: Q
authors.lastname: Du
authors.affiliation: Department of General Surgery, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Yao
authors.affiliation: Department of General Surgery, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China.
authors.forename: Ruiting
authors.initials: R
authors.lastname: Liu
keywords: Wnt signaling; gastric carcinoma; proliferation; receptor tyrosine kinase-like orphan receptor 2