氯离子通道蛋白ANO1在食管鳞癌细胞增殖中的作用机制研究

项目名称： 氯离子通道蛋白ANO1在食管鳞癌细胞增殖中的作用机制研究

项目编号： No.81460425

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 史志周

作者单位： 昆明理工大学

项目金额： 48万元

中文摘要： 目前临床上没有针对食管癌的靶向药，其原因是食管癌癌变过程中的驱动基因及其致癌机制尚不明确。我们前期发现氯离子通道蛋白ANO1在食管鳞癌组织中扩增且过表达，并且其过表达与淋巴结转移相关。功能研究发现敲降ANO1可显著抑制食管鳞癌细胞的增殖能力，并下调MCM7的表达。在敲降ANO1的食管鳞癌细胞中回复MCM7的表达可显著逆转敲降ANO1对细胞增殖的抑制作用，但ANO1如何调控MCM7的表达和ANO1的促增殖作用是否依赖其氯离子通道活性尚不清楚。基于此，本项目拟综合运用分子、细胞生物学技术，在细胞、动物模型及食管鳞癌组织水平对ANO1调控MCM7的分子机制，ANO1的siRNA和抑制剂的抑瘤作用以及ANO1、MCM7和相关蛋白与临床参数的关系进行研究，本项目的实施将揭示ANO1在食管鳞癌细胞增殖中的作用及详细调控机制，为阐明食管鳞癌的发生机理提供理论依据，为食管鳞癌的治疗提供候选分子靶点。

中文关键词： C06_食管肿瘤；ANO1；MCM7；增殖

英文摘要： Currently, no targeted drugs special for esophageal cancer are used in clinical practice, because the driven genes and tumorigenic mechanisms of esophageal cancer are unclear. Our previous study showed that chloride channel protein ANO1 was amplified and overexpressed in esophageal squamous cell carcinoma (ESCC), and its overexpression was significantly associated with lymph node metastasis. Knockdown of ANO1 in esophageal cancer cells could significantly inhibit cell proliferation in vitro and down-regulate the expression of MCM7. Restoration of MCM7 expression could rescue the inhibitory effect of ANO1 knockdown on cell proliferation. However, the mechanism of ANO1 regulating esophageal cancer cell proliferation via MCM7 and whether the promoting role of ANO1 on cell proliferation was dependent on its chloride channel function are still unknown. Basis on the preliminary findings, we will investigate the regulatory mechanisms between ANO1 and MCM7, inhibitory effects of ANO1 siRNA and its inhibitor on ESCC cells, and relationship between ANO1, MCM7, related proteins and clinical parameters. This project can reveal the molecular mechanisms of ESCC formation, and also provide candidate molecular targets for the therapy of ESCC.

英文关键词： esophageal cancer;ANO1;MCM7;proliferation