Arginine methylation of SHANK2 by PRMT7 promotes human breast cancer metastasis through activating endosomal FAK signalling
Authors: Guannan Wang
Dong-Xu Liu
Lingxia Liu
Hongyuan Li
Baiqu Huang
Jiayuan Liu
Jun Lu
Xiaoqing Liu
Yibo Wang
Lu Peng
Yingqi Liu
Lian Zhang
Lingling Li
Yu Zhang
Journal: eLife (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: FAK; PRMT7; SHANK2; cancer biology; cell biology
Affiliations: The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun, China, The Institute of Genetics and Cytology, Northeast Normal University, Changchun, China, Laboratory of Chemical Biology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, China, The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Northeast Normal University, Changhcun, China, The Centre for Biomedical and Chemical Sciences, School of Science, Faculty of Health and Environmental Sciences, Auckland University of Technology, Auckland, New Zealand

Abstract:  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. 

Retracted: Yes

PubPeer comments:
 Figure 5-E, Rab5 Talin image and EEA1 FAK image are the same. , 
 #1 Thank you very much for helping us find out the problem. I contacted with the first author and he did insert the incorrect image unintentionally. We are sending the detailed explaination to eLife for the mistake. Actually, based on our follow-up experiments, we feel that our original conclusion that PRMT7 directly catalyzes the SHANK2 di-methylation is incorrect. We have asked eLife to retact the article on 1, June, 2020. Thanks again for your comment. , 
 July 22 retraction: https: elifesciences.org articles 72188  We are retracting the eLife paper cited above in which we suggested that PRMT7 promoted breast cancer cell metastasis through di-methylating SHANK2 R240. After publication, an expert in the field of PRMTs noted that we did not provide in vitro methylation mapping data to demonstrate the direct methylation of SHANK2 by PRMT7. We re-performed experiments to detect the effect of PRMT5 on SHANK2 methylation, and the results indicate that PRMT5 might play an important role in SHANK2 di-methylation. Based on these results, we believe that the di-methylation of SHANK2 by PRMT7 might be dependent on PRMT5, which means our original conclusion that PRMT7 directly catalyses the SHANK2 di-methylation needs to be investigated further. Separately, a reader raised a concern on PubPeer about data presented in Figure 5E. We investigated this matter and examined the raw images carefully. We did insert the wrong image of EEA1 FAK in the vector group unintentionally. We have provided three independent replicates to the editors to explain the misuse of the image. Although the mistake does not affect the variation trend between multiple replications, we deeply apologize to readers. ,