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Automethylation of protein arginine methyltransferase 7 and its impact on breast cancer progression
Author(s) -
Geng Pengyu,
Zhang Yu,
Liu Xiaoqing,
Zhang Na,
Liu Yingqi,
Liu Xin,
Lin Cong,
Yan Xu,
Li Zhongwei,
Wang Guannan,
Li Yuxin,
Tan Jiang,
Liu DongXu,
Huang Baiqu,
Lu Jun
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201601196r
Subject(s) - methylation , methyltransferase , breast cancer , carcinogenesis , cancer research , protein arginine methyltransferase 5 , metastasis , arginine , in vivo , biology , cancer , microbiology and biotechnology , chemistry , biochemistry , genetics , gene , amino acid
Protein arginine methyltransferases (PRMTs) catalyze protein arginine methylation and are linked to carcinogenesis and metastasis. Some members of PRMTs have been found to undergo automethylation; however, the biologic significance of this self‐modification is not entirely clear. In this report, we demonstrate that R531 of PRMT7 is self‐methylated, both in vitro and in vivo . Automethylation of PRMT7 plays a key role in inducing the epithelial–mesenchymal transition (EMT) program and in promoting the migratory and invasive behavior of breast cancer cells. We also prove in a nude mouse model that expression of wild‐type PRMT7 in MCF7 breast cancer cells promotes metastasis in vivo , in contrast to the PRMT7 R531K mutant (a mimic of the unmethylated status). Moreover, our immunohistochemical data unravel a close link between PRMT7 automethylation and the clinical outcome of breast carcinomas. Mechanistically, we determine that loss of PRMT7 automethylation leads to the reduction of its recruitment to the E‐cadherin promoter by YY1, which consequently derepresses the E‐cadherin expression through decreasing the H4R3me2s level. The findings in this work define a novel post‐translational modification of PRMT7 that has a promoting impact on breast cancer metastasis.—Geng, P., Zhang, Y., Liu, X., Zhang, N., Liu, Y., Liu, X., Lin, C., Yan, X., Li, Z., Wang, G., Li, Y., Tan, J., Liu, D.‐X., Huang, B., Lu, J. Automethylation of protein arginine methyltransferase 7 and its impact on breast cancer progression. FASEB J. 31, 2287–2300 (2017). www.fasebj.org