Activation of EGFR-Aurora A induces loss of primary cilia in oral squamous cell carcinoma
Activation of EGFR-Aurora A induces loss of primary cilia in oral squamous cell carcinoma
复制标题
EGFR-Aurora A 的激活导致口腔鳞状细胞癌中初级纤毛的丧失
作者：
Yin Fengying;Chen Qian;Shi Yujie;Xu Hao;Huang Jie;Qing Maofeng;Zhong Liang;Li Jing;Xie Liang;Zeng Xin
初级纤毛，进化上保守的细胞器，涉及多种细胞功能，经常在各种癌症中丢失。方法采用免疫荧光染色法检测正常口腔黏膜、口腔白斑（OLK）及口腔鳞癌组织中的初级纤毛，并与正常口腔黏膜进行比较。从TCGA数据库中筛选OSCC中差异表达的纤毛基因。免疫组化分析用于验证感兴趣的蛋白质的表达和初级cilia之间的相关性，并在体外和体内进一步证明其对初级cilia的调节作用。多种纤毛基因在OSCC中异常表达，选择表皮生长因子受体（EGFR）-Aurora A信号进行进一步研究。在OLK和OSCC组织中观察到EGFR‐Aurora A平行增加。EGFR激活后，通过磷酸化Aurora A，诱导纤毛明显吸收。此外，Aurora A沉默显着恢复纤毛的表达和降低肿瘤的生长在vivo. ConclusionsEGFR-Aurora A的异常激活导致初级纤毛在口腔粘膜癌变的逐渐丧失。初级纤毛有可能成为口腔癌新的生物标志物和治疗靶点。
ObjectivePrimary cilia, evolutionally conserved organelles involving multiple cell functions, are frequently lost in various cancers. However, little is known about the role of primary cilia in oral squamous cell carcinoma (OSCC).MethodsImmunofluorescence staining was applied to detect primary cilia in normal, oral leukoplakia (OLK) and OSCC tissues. Differentially expressed ciliary genes of OSCC were screened from the TCGA database. Immunohistochemical analysis was used for validating the correlation between the expression of interested proteins and primary cilia, and their regulatory effect on primary cilia was further proved in vitro and in vivo.ResultsA significant decrease in cilia ratio was found in OLK, especially in OSCC. Multiple ciliary genes were abnormally expressed in OSCC and epidermal growth factor receptor (EGFR)‐Aurora A signaling was chosen for further study. A parallel increase of EGFR‐Aurora A was observed in OLK and OSCC tissues. Moreover, EGFR activation induced obvious cilia absorption by phosphorylating Aurora A. Besides, Aurora A silencing significantly restored ciliary expression and decreased tumor growth in vivo.ConclusionsThe abnormal activation of EGFR‐Aurora A leads to the gradual loss of primary cilia in oral mucosa carcinogenesis. Primary cilia have the potential to be new biomarkers and therapeutic targets of oral cancer.