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The role of R-spondin 1 through activating Wnt/β-catenin in the growth, survival and migration of ovarian cancer cells

Liu, Qiong, Zhao, Ying, Xing, Hui, Li, Lin, Li, Rongxia, Dai, Jie, Li, Quan, Fang, Shanshan
Gene 2019 v.689 pp. 124-130
animal ovaries, apoptosis, bioactive properties, cell lines, disease course, drug therapy, gene expression regulation, gene overexpression, genes, messenger RNA, neoplasm cells, ovarian neoplasms, protein content, recombinant proteins, small interfering RNA, tissues
Aberrant activation of the Wnt/β-catenin has been shown to promote progression in various cancers, including ovarian cancer. However, the molecular mechanisms involved in Wnt/β-catenin activation are not well elucidated. In the work, we identify that R-spondin 1 is an upstream regulator in Wnt/β-catenin pathway to promote growth, survival and migration in ovarian cancer cells. We observe the upregulation of transcript and protein levels of R-spondin 1 in ovarian cancer cell lines and tissues compared to normal counterparts. R-spondin 1 upregulation via genetic (overexpression) and pharmacological (recombinant protein) approaches facilitates growth and migration of normal ovarian cells. R-spondin 1 downregulation via siRNA knockdown decreases proliferation and migration, and induces apoptosis in ovarian cancer cells. In addition, recombinant R-spondin 1 protects ovarian cancer cell against chemotherapy whereas R-spondin 1 knockdown sensitizes ovarian cancer cell response to chemotherapy. Importantly, increased β-catenin activities and mRNA expression levels of Wnt/β-catenin-targeted genes are detected in normal ovarian cells overexpressing R-spondin 1. In contrast, R-spondin 1 inhibition suppresses Wnt/β-catenin signaling in ovarian cancer cells. We further identify that R-spondin 1 regulates ovarian cancer biological activities via activating Wnt/β-catenin. Our work is the first to highlight the critical roles of R-spondin 1 in ovarian cancer progression and chemoresistance. Our work also provides a proper understanding on the regulation of Wnt/β-catenin pathway in ovarian cancer.