Skip to Content
Merck
  • Arginine methylation of SHANK2 by PRMT7 promotes human breast cancer metastasis through activating endosomal FAK signalling.

Arginine methylation of SHANK2 by PRMT7 promotes human breast cancer metastasis through activating endosomal FAK signalling.

eLife (2020-08-28)
Yingqi Liu, Lingling Li, Xiaoqing Liu, Yibo Wang, Lingxia Liu, Lu Peng, Jiayuan Liu, Lian Zhang, Guannan Wang, Hongyuan Li, Dong-Xu Liu, Baiqu Huang, Jun Lu, Yu Zhang
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
2-Phenylindole, technical grade, 95%
Sigma-Aldrich
hEGF, EGF, recombinant, expressed in E. coli, lyophilized powder, suitable for cell culture
Sigma-Aldrich
Anti-Cortactin (p80/85) Antibody, clone 4F11, Alexa Fluor 488, clone 4F11, Upstate®, from mouse
Sigma-Aldrich
Anti-dimethyl-Arginine Antibody, symmetric (SYM10), serum, Upstate®
Sigma-Aldrich
Anti-PRMT5 Antibody, Upstate®, from rabbit
Sigma-Aldrich
Monoclonal Anti-HA antibody produced in mouse, clone HA-7, ascites fluid
Sigma-Aldrich
Cholera Toxin A Subunit from Vibrio cholerae, lyophilized powder
Sigma-Aldrich
Anti-β-Actin antibody, Mouse monoclonal, clone AC-15, purified from hybridoma cell culture
Sigma-Aldrich
Anti-Actin, α-Smooth Muscle antibody, Mouse monoclonal, clone 1A4, purified from hybridoma cell culture