转移是癌症致死的主要因素，癌细胞侵袭性的获得是癌症转移的先决条件。癌细胞侵袭性的增强常伴随着从相对高增殖低侵袭状态向低增殖高侵袭状态的转换，然而这种状态转换的分子机制还远未阐明。我们已发表的工作报道了精氨酸甲基转移酶PRMT7抑制乳腺癌细胞增殖，促进乳腺癌细胞侵袭及乳腺癌转移，提示PRMT7可能是促进乳腺癌由增殖型向侵袭型转换的重要因子。在此基础上，我们还发现PRMT7能够甲基化修饰多结构域蛋白shank2，这种修饰可能促进乳腺癌细胞增殖-侵袭状态的转换。本项目拟在以上工作基础上，阐明PRMT7通过甲基化shank2促进乳腺癌细胞由增殖型向侵袭型转换的分子机制，同时明确shank2的表达及其精氨酸甲基化修饰与乳腺癌进展和预后的关系。本项目的完成将提出精氨酸甲基化修饰在乳腺癌细胞由增殖型向侵袭型转换过程中作用的新机制，同时发现新的乳腺癌进展和预后相关靶标。

Metastasis is the leading cause of breast cancer-related death. The aggressive nature of breast cancer cells results from their intrinsic potential to dynamically switch from a high-proliferative/low invasive to a low-proliferative/high-invasive state. The mechanism of switch is far from clear. Results of our pre-paper reveal PRMT7 inhibites breast cancer cell proliferation, and we identify shank2 as a key effector of breast cancer development. Also, PRMT7 methylates shank2, and this methylation modification is necessary for breast cancer cell proliferation-matastasis switching. This study aims at the elucidation of the roles and mechanisms of shank2 and its arginine methylation modification by PRMT7 in regulation of breast cancer proliferation-matastasis switching. In addition, the relationship between shank2 expression and its arginine methylation modification and prognosis will also be determined. Prospectively, this study may lay down a basis for arginine methylation modification in breast cancer cells proliferation-matastasis switching, also provide a new therapeutic target of breast cancer.