SOX30抑制非小细胞肺癌转移的机制研究

项目名称： SOX30抑制非小细胞肺癌转移的机制研究

项目编号： No.81502551

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 韩飞

作者单位： 中国人民解放军第三军医大学

项目金额： 18万元

中文摘要： 转移是导致肿瘤治疗失败和死亡的最主要原因，鉴定并阐明重要基因在肿瘤转移中的机制对其临床治疗有重要意义。申请者前期首次证明了，SOX30是一个新的肿瘤抑制基因，通过转录激活p53信号促进肿瘤细胞凋亡。最近又发现，SOX30能够明显抑制非小细胞肺癌转移。更重要的是SOX30能够显著下调肿瘤转移重要基因MMP-7表达。这些数据提示，SOX30通过调控MMP-7发挥转移抑制的功能。但具体机制不清楚。为此，本项目将开展SOX30转移抑制功能在体确证和发挥作用的机制研究：第一、通过裸鼠移植瘤和SOX30敲除诱发瘤体内确证SOX30抑制肿瘤转移作用；第二、通过差异表达细胞和动物模型，从SOX30通过与MMP-7启动子直接结合和通过Wnt/β-catenin信号介导转录活性两方面，分析SOX30调控MMP-7转录表达发挥肿瘤转移抑制功能的具体机制。本研究将为肿瘤转移治疗提供新的靶点，具有潜在临床应用前景。

中文关键词： SOX30；转移抑制；MMP-7；分子机制；非小细胞肺癌

英文摘要： Metastasis is the main cause for failure of cancer treatment and tumor related death. Identification key genes and clarification the mechanism of these genes in tumor metastasis are very important for the clinical treatment of metastasis. In our previous study, we identified SOX30 as a novel tumor suppressor acting through directly regulation of p53 transcription in human lung cancer. Recently, we found that SOX30 is involved in non small cell lung cancer metastasis and acts as a putative tumor metastasis suppressor. More importantly, we provide strong evidence for the role of SOX30 as key events in suppressing metastatic potential is closely associated with attenuated MMP7. However, the molecular mechanism is unexplored. Here, we sought to verify the functional role in vivo using tumor xenograft in nude mice and chemical induced tumor in SOX30 knockout mice; to clarify the molecular mechanism of SOX30 as a tumor metastasis suppressor from regulation of the MMP-7 transcription activity through directly binding to MMP-7 promoter and the Wnt/β-catenin signaling mediated transcriptional activity in cell and animal model constructed. Understanding the key factors in tumor metastasis processes is crucial to the development of novel anticancer therapies, which might have an important significance in the medical theory and clinical treatment.

英文关键词： SOX30;metastasis suppressor;MMP-7;Molecular mechanism;Non small cell lung cancer