MYG1不同亚细胞定位多层次协同调控结直肠癌侵袭转移的分子机制

课题组前期研究发现MYG1在结直肠癌中表达上调，其表达失调与结直肠癌的侵袭、转移及临床预后相关。其过表达可增强结直肠癌细胞的增殖、迁移及侵袭能力，并与结肠癌EMT密切相关。分析显示MYG1亚细胞定位具有不同功能途径，进一步利用CoIP 结合质谱分析发现MYG1在线粒体内能与细胞色素C结合，并通过其依赖的线粒体功能途径诱导细胞自噬介导EMT，是MYG1实现其调控结直肠癌侵袭转移的途径之一。据此我们提出，MYG1通过细胞胞核和线粒体不同亚细胞定位，多层次介导EMT的发生，从而协同诱导结直肠癌侵袭和转移。本项目拟采用分子病理及分子生物学方法，结合体内外研究，全方位阐明MYG1促进结直肠癌侵袭转移的作用机制，为深入理解结直肠癌发病机理提供新依据与新思路。

Metastatic spreading is the main cause of cancer-related deaths. We previously demonstrated that MYG1 expression was significantly increased in colorectal carcinoma (CRC), which was correlated with invasion, metastasis and clinical prognosis in patients with CRC. Up-regulation of MYG1 significantly enhanced proliferation, migration and invasiveness of CRC cells in vitro and involved in epithelial-mesenchymal transition (EMT) process. Co-immunoprecipitation (CoIP) assays combined with mass spectrography revealed that MYG1 could bind to CYCS directly in mitochondria and regulate cell autophagy-mediated EMT through its dependent mitochondrial function pathway. Therefore, we proposed that MYG1 may occur in mitochondrion and nuclear and induced EMT at the multi-levels and promoted CRC metastasis. The research will uncover the pathway of MYG1 effects on CRC, and will provide basic knowledge establishing MYG1 as a novel target for clinical therapy of patients with advanced CRC.