Abstract 3813: Activation of EGFR induces loss of primary cilia in oral mucosa carcinogenesis

Abstract

Abstract Objective: Primary cilia are evolutionally conserved cell structures involving multiple cell functions by sensing extracellular signals. Loss of primary cilia is frequently observed in various cancer types, suggesting that the absence of this organelle may promote tumorigenesis. However, little is known about the role of primary cilia in oral premalignant lesions and oral squamous cell carcinoma (OSCC). Materials and Methods: Immunofluosense staining was carried out to detect the incidence of primary cilia in every stages of oral carcinogenesis from normal to OSCC. Immunohistochemical analysis was used for validating the correlation between the ciliary incidence and the expression level of EGFR in the oral carcinogenesis. Furthermore, the change of primary cilia was detected by activating and inhibiting the EGFR pathway activity in vitro. Results: A significant decrease in the percentage of ciliated cells was found on both oral leukoplakia (OLK), as well as OSCC tissues, compared to normal oral mucosa epithelium, and this loss of cilia was independent of the increased proliferative index. A parallel increase of EGFR activity was observed in OLK and OSCC tissues. In addition, EGF stimulation induced obvious primary cilia absorption, whereas inhibition of EGFR by gefitinib significantly restored cilia formation in vitro. We further found that the activation of EGFR resulted in the phosphorylation of AURKA, a pivotal kinase promoting disassembly of primary cilia. Conclusion: EGFR-AURKA pathway might be a critical regulator of ciliary loss in the carcinogenesis of oral mucosa. This may provide insight into the development of new therapeutic strategies to prevent oral premalignant lesions from becoming malignant. Citation Format: Fengg yin, Zihao Wei, Jing Li, Liang Xie, Qianming Chen. Activation of EGFR induces loss of primary cilia in oral mucosa carcinogenesis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3813.