SOX2 Expression Associates with Stem Cell State in Human Ovarian Carcinoma

Abstract

The SRY-related HMG-box family of transcription factors member SOX2 regulates stemness and pluripotency in embryonic stem cells and plays important roles during early embryogenesis. More recently, SOX2 expression was documented in several tumor types including ovarian carcinoma, suggesting an involvement of SOX2 in regulation of cancer stem cells (CSC). Intriguingly, however, studies exploring the predictive value of SOX2 protein expression with respect to histopathologic and clinical parameters report contradictory results in individual tumors, indicating that SOX2 may play tumor-specific roles. In this report, we analyze the functional relevance of SOX2 expression in human ovarian carcinoma. We report that in human serous ovarian carcinoma (SOC) cells, SOX2 expression increases the expression of CSC markers, the potential to form tumor spheres, and the in vivo tumor-initiating capacity, while leaving cellular proliferation unaltered. Moreover, SOX2-expressing cells display enhanced apoptosis resistance in response to conventional chemotherapies and TRAIL. Hence, our data show that SOX2 associates with stem cell state in ovarian carcinoma and induction of SOX2 imposes CSC properties on SOC cells. We propose the existence of SOX2-expressing ovarian CSCs as a mechanism of tumor aggressiveness and therapy resistance in human SOC. Cancer Res; 73(17); 5544-55. Ó2013 AACR.

miR-488 acts as a tumor suppressor gene in gastric cancer

“…SOX2, a member of SRY-related HMG-box transcription factors families, is a well-established regulator of cell differentiation and development [27,28]. More than that, accumulating studies suggest that SOX2 acts as an oncogene in some cancers, such as skin squamous-cell carcinoma [29,30], lung squamouscell carcinoma [31,32], ovarian carcinoma [33], osteosarcomas [34] and glioblastoma [35].…”

Embryonic Stem Cells and Oncogenes

“…Sox2 expression in breast cancer enhances cancer stem cell-like properties [40]. Sox2 is also reportedly involved in regulation of cancer stem-like cells in ovarian carcinoma [41].…”

Novel AKT phosphorylation sites identified in the pluripotency factors OCT4, SOX2 and KLF4

“…2,3 OSKM transcription factors are involved not only in pluripotency and differentiation of stem cells, but also in tumorigenesis. [4][5][6][7][8][9][10][11] The expression of OSKM factors is controlled in a coordinated manner by several feedback loops and requires a tight regulation to maintain stem cell potential. A slight change in the amount of the proteins can lead to drastic alterations in cell fate that may eventually result in tumorigenesis.…”