Abstract 4380: CD133/prominin-1 modulates epithelial-mesenchymal transition, stemness and tumorigenicity of oral squamous cell carcinoma-derived cancer initiating

Abstract

Abstract Background: Oral squamous carcinoma cell (OSCC) is a lethal cancer with clinical, pathological, phenotypical and biological heterogeneity. Tumor initiating cells (TICs), which are responsible for tumor growth and coupled with epithelial-mesenchymal transition (EMT), have been identified. We have also identified the subpopulation of oral cancer derived tumor initiating cells (OC-TICs), and observed the upregulation of CD133 in OC-TICs. Others demonstrate that CD133 is phosphorylated by Src and Fyn tyrosine kinases. However, the molecular function of CD133 in OC-TICs remains unclear. Herein we determined the critical role of CD133, an important TICs marker, in the maintenance of stemness characteristics and tumorigenic phenotype of OC-TICs. Methods: Stable overexpression and knockdown of CD133 expression in OSCCs and OC-TICs was achieved by lentiviral-mediated system. Consequently, we elucidated the epithelial-mesenchymal transition, the stemness properties and tumorigenicity of OSCCs and OC-TICs with CD133 down-regulation or overexpression, respectively. Consequently, we investigated the role of Src and and Fyn tyrosine kinases in CD133 mediated signaling pathway. Results: Stable over-expression of CD133 induced epithelial-mesenchymal transition, enhanced tumorigenicity and enhanced the TICs properties in OSCCs. In contrast, lentiviral knockdown of CD133 significantly reduced the self-renewal ability, side population cells, and stemness genes in OC-TICs. Additionally, down-regulation of CD133 enhanced the differentiation capability but inversely diminished “stemness” gene expression of OC-TICs. Of note, knockdown of CD133 lessened tumorigenicity of OC-TICs both in vitro and in vivo. Furthermore, over-expression of CD133 increased phosphorylation of Src and Erk1/2. Conclusion: We showed that CD133 contributes to the epithelial-mesenchymal transition and the maintenance of stemness and tumorigenicity of OC-TICs. In addition, Src and Erk1/2 activation was involved in CD133 modulating phenotype. Overall, silencing CD133 might be a potential therapeutic target for OSCC by eliminating TICs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4380. doi:10.1158/1538-7445.AM2011-4380