SOX9/NFIA promotes human ovarian cancer metastasis through the Wnt/β-catenin signaling pathway

Abstract

To our knowledge, Sex-determining Region Y box 9 (SOX9) has been in connection with a wide range of human cancers. Nevertheless, there remains uncertainty regarding SOX9's role in metastasizing ovarian cancer. In our study, SOX9 was investigated in relation to tumor metastasis in ovarian cancer as well as its potential molecular mechanisms. First, we exhibited an apparent higher expression of SOX9 in ovarian cancer tissues and cells than in normative ones, and the prognosis of patients whose SOX9 levels were high was markedly lower than that of patients whose SOX9 levels were low. Besides, highly expressed SOX9 was correlated with high grade serous carcinoma, poor tumor differentiation, high serum CA125 and lymph node metastasis. Second, SOX9 knockdown exhibited striking inhibition of the migration and invasive ability of ovarian cancer cells, whereas SOX9 overexpression had an inverse role. At the same time, SOX9 could promote ovarian cancer intraperitoneal metastasis in a nude mice in the vivo. In a similar way, SOX9 knockdown dramatically decreased the expression of nuclear factor I-A (NFIA), β-catenin as well as N-cadherin but had an increased in E-cadherin expression, as opposed to the results when SOX9 was overexpressed. Furthermore, NFIA silencing inhibited the expression of NFIA, β-catenin and N-cadherin, in the same way that E-cadherin expression was promoted. In conclusion, this study shows that SOX9 has a promotional effect on human ovarian cancer and that SOX9 promotes the metastasis of tumors by upregulating NFIA and activating on a Wnt/β-catenin signal pathway. SOX9 could be a novel focus for earlier diagnosis, therapy and prospective evaluation in ovarian cancer.