Abstract
The Rab GTPase family protein Rab14 has been implicated in cancer development. However, its clinical significance in ovarian cancers and its biological effects have not been examined. The present study aims to examine the clinical significance, biological roles, and molecular mechanism of Rab14 in ovarian cancer progression. We examined expression pattern of Rab14 in 122 cases of ovarian cancer specimens using immunohistochemistry and found Rab14 overexpression correlated with FIGO stage (p = 0.0041). We depleted Rab14 in SKOV3 cells using siRNA and overexpressed Rab14 in SW626 cells. Knockdown of Rab14 inhibited cell growth and invasion while its overexpression facilitated cell growth and invasion. In addition, Rab14 overexpression increased paclitaxel resistance in SW626 cells while its depletion reduced drug resistance. Then, we investigated the role of Rab14 in the regulation of WNT/β-catenin signaling, demonstrating Rab14 overexpression regulated GSK3β phosphorylation and nuclear β-catenin accumulation. Rab14 depletion inhibited while its overexpression enhanced TCF transcriptional activity with corresponding change of Wnt target genes including MMP7 and c-myc. Wnt inhibitor abolished the effect of Rab14 on cell proliferation and Wnt target genes. In conclusion, the present study demonstrated that Rab14 promotes aggressiveness of ovarian cancer cell through, at least partly, Wnt signaling pathway.