The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun, China
Lingling Li
The Institute of Genetics and Cytology, Northeast Normal University, Changchun, China
Xiaoqing Liu
The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun, China
Yibo Wang
Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, China
Lingxia Liu
The Institute of Genetics and Cytology, Northeast Normal University, Changchun, China
Lu Peng
The Institute of Genetics and Cytology, Northeast Normal University, Changchun, China
Jiayuan Liu
The Institute of Genetics and Cytology, Northeast Normal University, Changchun, China
Lian Zhang
The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun, China
Guannan Wang
The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun, China
Hongyuan Li
Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, China
Dong-Xu Liu
The Centre for Biomedical and Chemical Sciences, School of Science, Faculty of Health and Environmental Sciences, Auckland University of Technology, Auckland, New Zealand
Baiqu Huang
The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun, China
Jun Lu
The Institute of Genetics and Cytology, Northeast Normal University, Changchun, China
Arginine methyltransferase PRMT7 is associated with human breast cancer metastasis. Endosomal FAK signalling is critical for cancer cell migration. Here we identified the pivotal roles of PRMT7 in promoting endosomal FAK signalling activation during breast cancer metastasis. PRMT7 exerted its functions through binding to scaffold protein SHANK2 and catalyzing di-methylation of SHANK2 at R240. SHANK2 R240 methylation exposed ANK domain by disrupting its SPN-ANK domain blockade, promoting in co-accumulation of dynamin2, talin, FAK, cortactin with SHANK2 on endosomes. In addition, SHANK2 R240 methylation activated endosomal FAK/cortactin signals in vitro and in vivo. Consistently, all the levels of PRMT7, methylated SHANK2, FAK Y397 phosphorylation and cortactin Y421 phosphorylation were correlated with aggressive clinical breast cancer tissues. These findings characterize the PRMT7-dependent SHANK2 methylation as a key player in mediating endosomal FAK signals activation, also point to the value of SHANK2 R240 methylation as a target for breast cancer metastasis.
