Inactivation of Wnt-LRP5 signaling suppresses the proliferation and migration of ovarian cancer cells.

Abstract

BackgroundOvarian cancer (OCa) is the most lethal gynecological malignant tumor, with few or no specific symptoms in its early stage. There are many signaling pathways involved in the process of OCa progression, among which the highly complex Wnt signaling pathway plays a unique role in the occurrence and development of OCa because of its functions of regulating gene expression, cell proliferation, migration, and invasion. Lipoprotein associated receptor protein 5/6 (LRP5/6) binds to activate this key pathway. Therefore, it is very important to study the mechanism of Wnt-LRP5 signaling pathway in the proliferation and migration of OCa.MethodsIn the present study, we have investigated the role of Wnt-LRP5 signaling pathway in OCa proliferation and migration for the first time using the dominant negative plasmid of LRP5 (DN-LRP5) and human OCa cells HO8910PM plus in a mouse model.ResultsOur data showed inactivation of LRP5 resulted in shift of epithelial-mesenchymal transition (EMT), rearrangement of the cytoskeleton, lowered activity of pro-proliferation and pro-migration cancer signaling pathways including Akt, p38 and NF-κB, eventually decreased proliferation and migration of OCa cells HO8910PM in vitro. Moreover, in vivo OCa-DN-LRP5 mouse model developed significantly smaller tumors as determined by inoculation of HO8910PM-DN-LRP5 cells into nude mice.ConclusionsCollectively, our results demonstrate the dominant role of Wnt-LRP5 in OCa proliferation and migration and its potential as a valuable therapeutic target.