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

Abstract

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.

• Authors: Qiong Liu, Ying Zhao, Hui Xing, Lin Li, Rongxia Li, Jie Dai, Quan Li, Shanshan Fang
• Journal: Gene (Gene) Vol. 689 Pg. 124-130 (Mar 20 2019) ISSN: 1879-0038 [Electronic] Netherlands
• PMID: 30572097 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• RSPO1 protein, human
• Thrombospondins
• beta Catenin

Topics

• Carcinoma, Ovarian Epithelial (drug therapy, genetics, pathology)
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Cell Survival (genetics)
• Cells, Cultured
• Drug Resistance, Neoplasm (genetics)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Ovarian Neoplasms (drug therapy, genetics, pathology)
• Thrombospondins (genetics, physiology)
• Wnt Signaling Pathway (genetics)
• beta Catenin (metabolism)