Role of <i>VOPP1</i> in regulation of Paclitaxel response and EMT process during ovarian tumor progression.

Ovarian cancer (OC) is one of the most common malignancies of the genitourinary system in women that has a high mortality rate worldwide. Drug resistance and tumor relapse are the main causes of high mortality rate in OC patients. Therefore, investigation of the molecular mechanisms involved in OC progression can be valuable to introduce effective therapeutic targets for these patients. Epithelial-mesenchymal transition (EMT) as a key regulator of tumor relapse and drug resistance can be regulated by different signaling pathways such as WNT and NOTCH. <i>VOPP1</i> is an activator of NF-κB pathway during tumor progression. Considering the importance of cross talks between different signaling pathways during tumor progression, we assessed the role of <i>VOPP1</i> in OC progression through the modulation of WNT and NOTCH pathways. The expression levels of components of WNT and NOTCH signaling pathways, as well as the EMT process, were evaluated in <i>VOPP1</i>-induced A2780 cells compared to control cells. Role of <i>VOPP1</i> in OC invasiveness was also assessed through migration and drug resistance assays. <i>VOPP1</i> inhibited EMT process and NOTCH and WNT pathways in A2780 cells. <i>VOPP1</i> also significantly reduced cell migration (<i>p</i>=0.04) and paclitaxel (PTX) resistance in A2780 cells (<i>p</i><0.0001). <i>VOPP1</i> reduced ovarian tumor cell migration and PTX resistance via regulation of NOTCH and WNT mediated EMT process. Therefore, it can be suggested as a novel therapeutic target in OC patients following further animal studies and clinical trials.