An integrated analysis identifies STAT4 as a key regulator of ovarian cancer metastasis

摘要: Epithelial ovarian cancer (EOC) is one of the most common gynecological cancers, with diagnosis often at a late stage. Metastasis major cause death in patients EOC, but underlying molecular mechanisms remain obscure. Here, we utilized an integrated approach to find potential key transcription factors involved metastasis and identified STAT4 as critical player metastasis. We found that activated was overexpressed epithelial cells overexpression associated poor outcome patients, which promoted both vivo vitro. Although mediated EOC via inducing epithelial-to-mesenchymal transition (EMT) vivo, failed induce EMT directly vitro, suggesting might mediate process cancer-stroma interactions. Further functional analysis revealed induced normal omental fibroblasts adipose- bone marrow-derived mesenchymal stem obtain cancer-associated (CAF)-like features induction tumor-derived Wnt7a. Reciprocally, increased production CAF-induced CXCL12, IL6 VEGFA within tumor microenvironment could enable peritoneal program. In summary, our study established model promotes Wnt7a-induced activation CAFs.