Partitioning defective 6 homolog alpha (PARD6A) encodes an important molecular scaffold protein which has been mostly studied in cell polarization and differentiation. However, little is known about the roles and molecular mechanisms of PARD6A in cancers, especially in ovarian cancer. In this study, correlation between PARD6A and ovarian cancers clinically was examined firstly using paraffin sections from ovarian cancer patients. Furthermore, the biological functions of PARD6A were identified in ovarian cancers by silencing or overexpressing PARD6A gene in SKOV3 and A2780 ovarian cancer cell lines. Finally, the effects of silencing PARD6A in a xenograft metastatic mouse model of ovarian cancers were studied. PARD6A gene was found to be highly expressed in epithelial ovarian cancer cell lines SKOV3 and A2780 and highly correlated to serous and mucuous ovarian cancers. Silencing PARD6A can inhibit cell migration and invasion, attenuate cell adhersion ability and change cell polarity; overexpression of PARD6A promotes anchorage independent growth, cell migration, and invasion. We further verified that silencing of PARD6A can inhibit the metastasis of ovarian cancer cell SKOV3 in mice through mouse tumor lung metastasis model experiments. Mechanistically, PARD6A was found to be involved in Cdc42 and RhoA mediated signaling pathways to affect cell migration and invasion. In sum, targeted therapies against PARD6A might be potential in ovarian cancer treatment.
Acknowledgments
This work was supported by the National Natural Science Foundation 81672582 (to H. Liu) and 31471294 and 31771521 (to Z. Tu); Natural Science Foundation of Jiangsu Province for Distinguished Young Scholars BK20160013 (to H. Liu); Natural Science Foundation of Jiangsu Province BE2016718 (to Z. Tu); Youngth Talents of Science and Technology by Jiangsu Association for Science and Technology (to H. Liu); Six Talent Peak Project from Government of Jiangsu Province 2015-SWYY-019 (to H. Liu) and 2016-SWYY-011 (to Z. Tu).