Ovarian cancer metastasis is one of the reasons for a low 5-year survival rate. Spheroids, 3D growing cell clusters, are now recognized as playing a major role in ovarian cancer metastasis. We have found that the STAT3 signaling pathway is enhanced in ovarian cancer spheroids. Moreover, the STAT3 signaling pathway is necessary for spheroid growth. The first step in ovarian cancer metastasis mediated by spheroids is mesothelial clearance, and we have found that STAT3 also plays a role in ovarian cancer mesothelial clearance. Therefore, our preliminary studies suggest that STAT3 is important for spheroid mediated metastasis; however, the mechanism(s) of STAT3 promoting spheroid growth and mesothelial clearance are currently unknown, and key downstream target genes involved in these mechanisms remain unidentified. Our overall hypothesis is that targeting key downstream components of the STAT3 signaling pathway will inhibit spheroid growth and metastasis. Thus, identifying these genes would provide starting points for future ovarian cancer therapy. To begin to identify these genes, we propose the following specific aims: 1) to identify the STAT3 target genes expressed in spheroids using a combination of RNA- and ChIPseq and 2) to develop an in vitro assay to measure dynamic gene expression changes during ovarian cancer metastasis.
