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Abstract
Abstract Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. We have shown that c-Fos was highly up-regulated in the HNSCC sphere forming cells. However, upregulation of c-Fos for the biology of HNSCC-CSCs remains unknown. In this study, we investigated the role of c-Fos in renewal of stemness of HNSCC and tumor growth. We demonstrated that c-Fos overexpression enhanced the epithelial-mesenchymal transition (EMT) state and expression of CSC markers (Nanog, c-Myc, Sox2 and Notch1). Ectopic expression of c-Fos in HNSCC cells also display increased number of sphere formation. We further observed that overexpression of c-Fos increased the expression of pERK and cyclin D1 in HNSCC cells. Knockdown of c-Fos in Cal27 cells impaired sphere formation. Next we examine the effect of c-Fos expression in vivo. For this, we established stable HNSCC cell line (MDA1386Tu cells) where c-Fos gene is ectopically expressed. Our results demonstrated that exogenous expression of c-Fos in non-tumorigenic MDA1386Tu cells makes these cells tumorigenic in nude mice. Further, subcutaneous transplantation of c-Fos overexpressing Cal27 cells (tumorigenic) into immunocompromised mice enhanced tumor growth as compared to parental cells. Taken together, our results strongly demonstrated a novel role of c-Fos as a regulator of EMT and cancer stem cell reprogramming in HNSCC cells. Collectively, our results offer that c-Fos may be a new target for developing therapeutic strategies against HNSCC. Citation Format: Ratna B. Ray. c-Fos: A new player in promotion of cancer stem-like cell properties in head and neck squamous cell carcinoma [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 66.
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