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Arginine methylation‐dependent LSD1 stability promotes invasion and metastasis of breast cancer
Author(s) -
Liu Jiwei,
Feng Jingxin,
Li Lili,
Lin Luyao,
Ji Jiafei,
Lin Cong,
Liu Lingxia,
Zhang Na,
Duan Dandan,
Li Zhongwei,
Huang Baiqu,
Zhang Yu,
Lu Jun
Publication year - 2019
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201948597
Subject(s) - demethylase , cancer research , methylation , breast cancer , metastasis , biology , arginine , histone methylation , vimentin , histone , cancer , dna methylation , biochemistry , immunology , gene expression , genetics , immunohistochemistry , gene , amino acid
Histone lysine demethylase 1 ( LSD 1), the first identified histone demethylase, is overexpressed in multiple tumor types, including breast cancer. However, the mechanisms that cause LSD 1 dysregulation in breast cancer remain largely unclear. Here, we report that protein arginine methyltransferase 4 ( PRMT 4 or CARM 1) dimethylates LSD 1 at R838, which promotes the binding of the deubiquitinase USP 7, resulting in the deubiquitination and stabilization of LSD 1. Moreover, CARM 1‐ and USP 7‐dependent LSD 1 stabilization plays a key role in repressing E‐cadherin and activating vimentin transcription through promoter H3K4me2 and H3K9me2 demethylation, respectively, which promotes invasion and metastasis of breast cancer cells. Consistently, LSD 1 arginine methylation levels correlate with tumor grade in human malignant breast carcinoma samples. Our findings unveil a unique mechanism controlling LSD 1 stability by arginine methylation, also highlighting the role of the CARM 1‐ USP 7‐ LSD 1 axis in breast cancer progression.