DACT1 Is Involved In Type Ⅰ Epithelial Ovarian Carcinoma Proliferation And Mobility

Object Recently epithelial ovarian carcinoma(EOC) has been broadly classified as two categories: type I and type II. Although more than half of type I EOC patients could be diagnosed at early stages, a fraction of the tumors show invasive growth and makes the recurrent and metastatic cases. The purpose of the research is to explore the expression of DACT1(Dapper Antagonist of Catenin-1) in EOC and to investigate the effect of DACT1 on the malignant phenotypes of type I EOC and the involvement of DACT1 in the pathogenesis of type I EOC.Methods The expression of DACT1 in type I and type II ovarian cancer cell lines and tissues were detected by RT-PCR and immunohistochemistry. 3AO cells which arise from a patient with primary mucinous adenocarcinoma and express very low endogenous levels of DACT1, were transfected by the lentivirus carrying full-length DACT1, and experiment in vivo and vitro were performed to analyze cell proliferation and mobility. Key regulatory molecules in Wnt signaling were detected by Western Blot and F-actin was detected by immunofluorescence.Results Expression of DACT1 in EOC was significantly lower than that in normal ovarian tissues, especially in type I EOC. Forced expression of DACT1 significantly inhibited the proliferation, migration and invasion capacity of 3AO, and the tumorigenesis and intraperitoneal dissemination. Activity of Wnt signaling was significantly attenuated and specialized membrane structure in cytoskeleton such as lamellipodia in 3AO was decreased after DACT1 expression recovery.Conclusion DACT1 is a negative regulator of Wnt signaling and it may inhibit cell proliferation, mobility and tumorigenesis in type I ovarian cancer cell line 3AO through suppressing the activity of Wnt signaling. Its low expression may be involved in the pathogenesis of type I EOC.