Background: Head and Neck squamous cell carcinoma (HNSCC) is a lethal cancer with clinical, pathological, phenotypical and biological heterogeneity. Cancer initiating cells (CICs) exhibit self-renewal and promote tumor progression capacity. We have also identified the subpopulation of head and neck cancer initiating cells (HN-CICs), and observed the upregulation of Glucose Transporter 3(Glut3) in HN-CICs by differential systemic analyses. However, the role of Glut3 in HN-CICs metabolism alternation remains unclear. Herein we determined the critical role of Glut3, a novel CICs marker, in the maintenance of stemness characteristics and tumorigenic phenotype of HN-CICs. Methods: Stable overexpression and knockdown of Glut3 expression in HNSCCs and HN-CICs was achieved by lentiviral-mediated system. Consequently, we elucidated the stemness properties and tumorigenicity of HNSCCs and HN-CICs with Glut3 down-regulation. Consequently, we investigated the role of Glut3 in metabolism regulation of cancer initiation cells. Results: Lentiviral knockdown of Glut3 significantly reduced the self-renewal ability and cancer initiation cell marker Grp78 expression in HN-CICs. Additionally, down-regulation of Glut3 enhanced the differentiation capability but inversely diminished “stemness” gene expression of HN-CICs. Of note, knockdown of Glut3 lessened tumorigenicity of HN-CICs both in vitro. Conclusion: We showed that Glut3 contributes to the maintenance of stemness and tumorigenicity of HN-CICs. In addition, the expression of Glut3 was involved in HN-CICs metabolism. Overall, silencing Glut3 might be a potential therapeutic target for HNSCC by eliminating CICs.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3338. doi:1538-7445.AM2012-3338