Abstract 2538: The emerging role of SOX2 in cancer cell plasticity and EGFR-TKI resistance

Abstract

Abstract Activating mutations in the epidermal growth factor receptor (EGFR) lead to the aberrant growth of lung adenocarcinoma while endowing cancer cells with sensitivity to EGFR-tyrosine kinase inhibitors (TKIs). Nonetheless, EGFR-TKI resistance often occurs in less than one year. The intriguing phenomenon that cancer cells have biological features similar to stem cells suggests that cancer and stem cells may share the same regulatory signaling pathway, but the involvement of stem cell signaling in EGFR-TKI resistance is not clear. Herein, we observed that SOX2, a master transcriptional factor controlling self-renewal of lung stem cells, was highly expressed in lung adenocarcinoma and inversely correlated with epithelial-to-mesenchymal transition (EMT). Clonogenic analysis showed that SOX2-silenecing attenuated cell growth in EGFR-mutated lung cancer cells. The selection of EGFR-TKI resistant HCC827 (delE746_A750) cells induced EMT while attenuating the expression of SOX2 and spheroid forming ability. Preselection of HCC827 (delE746_A750) cells with EMT features endowed cells with TKI resistance but suppressed SOX2 expression. Pharmacological inhibition of HDACs in EGFR-mutated lung cancer cells attenuated SOX2 expression but induced EMT, thus enhancing the development of EGFR-TKI resistance. Our findings support the notion that the switching expression between SOX2 and EMT plays a critical role in EGFR-TKI resistance, with the potential as biomarkers for lung cancer prediction. Citation Format: Yu-Fan Chiu, Ming-Han Kuo, An-Chun Lee, Yu-Ting Chou. The emerging role of SOX2 in cancer cell plasticity and EGFR-TKI resistance. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2538.