Abstract

<div>Abstract<p>The SRY-related HMG-box family of transcription factors member <i>SOX2</i> regulates stemness and pluripotency in embryonic stem cells and plays important roles during early embryogenesis. More recently, <i>SOX2</i> expression was documented in several tumor types including ovarian carcinoma, suggesting an involvement of <i>SOX2</i> 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 <i>SOX2</i> 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, <i>SOX2</i> expression increases the expression of CSC markers, the potential to form tumor spheres, and the <i>in vivo</i> tumor-initiating capacity, while leaving cellular proliferation unaltered. Moreover, <i>SOX2</i>-expressing cells display enhanced apoptosis resistance in response to conventional chemotherapies and TRAIL. Hence, our data show that <i>SOX2</i> associates with stem cell state in ovarian carcinoma and induction of <i>SOX2</i> imposes CSC properties on SOC cells. We propose the existence of <i>SOX2</i>-expressing ovarian CSCs as a mechanism of tumor aggressiveness and therapy resistance in human SOC. <i>Cancer Res; 73(17); 5544–55. ©2013 AACR</i>.</p></div>

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