Abstract
Abstract Anoctamin-1 (ANO1), also known as TMEM16A, is a Ca2+-activated chloride channel known to mediate a number of physiologic functions such as mediating acute and chronic pain and regulating blood vessels and airway smooth muscle. In particular, ANO1 expression is amplified in a variety of cancers, and overexpression of ANO1 is not favorable for clinical prognosis. Previous studies have reported that ANO1 is associated with tumorigenesis, proliferation, migration, and invasion of cancer cells, but the mechanism is not clear yet. In this study, we examined role of ANO1 in the maintenance of stemness and radio-resistance in glioma stem cells (GSCs). Knockdown of ANO1 with shRNA and treatment of ANO1 specific inhibitors (CaCCAo1 and TAO1) suppressed the expression of Notch intracellular domain, Nestin and EGFRvIII and decreased self-renewal activity and invasion in GSCs. Suppression of ANO1 increased radiation sensitivity by inducing ROS-mediated GSCs death. However, inhibition of chloride channel activity, the main function of ANO1, was found to be unaffected in this event. Interestingly, we found that ANO1 retained stemness by direct binding to EGFRvIII, which is specifically expressed in GSCs, and that the chaperone property of ANO1 function may affect the stability of EGFRvIII. In intracranial mouse model of GSCs, knockdown of ANO1 increased the survival rate of mice by suppressing tumor formation. Taken together, we suggest that ANO1 is a crucial molecule involved in the maintenance of stemness and radiation resistance in GSCs and may be a good therapeutic target for treating glioblastoma. Citation Format: Dae-Hee Lee, Hee-Jin Kim, Jeong-Yub Kim, Jea-Yong Park, Myung-Jin Park. ANO1 confers the maintenance of stemness and radioresistance in glioma stem cells by stabilizing EGFRvIII [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1137.
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