SOS1 promotes epithelial-mesenchymal transition of Epithelial Ovarian Cancer(EOC) cells through AKT independent NF-κB signaling pathway

We aimed to explore the role and mechanism of SOS1 (Son of sevenless homolog 1) in malignant behaviors of epithelial ovarian cancer (EOC) cells Hey with high metastatic potential. Firstly, compared with Hey-WT (wild type) and Hey-NT (none targeted) cells, Hey-SOS1i cells showed decreased polarities, disorders in cytoskeleton arrangement. Numbers of transwell migrated, invaded, intravasation cells and extravasated cells were decreased significantly. Hey-NT cells and Hey-SOS1i cells were employed to establish a peritoneal dissemination model in nude mice. Hey-SOS1i cells formed less implantation metastatic foci in the abdominal cavity than Hey-NT cells, especially on the intestine and diaphragm in the 5(th) week after the tumor cells were injected intraperitoneally. SOS1 knockdown in Hey cells resulted in increased E-cadherin and decreased Vimentin, N-cadherin, MMP2, and MMP9, together with reduced Snail and activation of NF-κB pathway. Together, these results suggest SOS1 might induce EMT through activating AKT independent NF-κB pathway and the transcriptive activity of Snail, and subsequently regulate the cytoskeleton reprogramming and cell motility of Hey, one of EOC cells with high metastatic potential. This may provide some new targets for the treatment of ovarian cancer with high metastatic potential.