JAC1 suppresses proliferation of breast cancer through the JWA/p38/SMURF1/HER2 signaling

被引：14
|
作者：
Ren, Yanlin [1 ,2 ,5 ]
Chen, Dongyin [3 ]
Zhai, Zurong [1 ,2 ]
Chen, Junjie [1 ,2 ]
Li, Aiping [1 ,2 ]
Liang, Yan [2 ,4 ]
Zhou, Jianwei [1 ,2 ]
机构：
[1] Nanjing Med Univ, Sch Publ Hlth, Ctr Global Hlth, Dept Mol Cell Biol & Toxicol, Nanjing 211166, Peoples R China
[2] Nanjing Med Univ, Collaborat Innovat Ctr Canc Med, Jiangsu Key Lab Canc Biomarkers Prevent & Treatm, Nanjing 211166, Peoples R China
[3] Nanjing Med Univ, Sch Pharm, Dept Med Chem, Nanjing 211166, Peoples R China
[4] Nanjing Med Univ, Dept Oncol, Affiliated Hosp 1, Nanjing 211166, Peoples R China
[5] Nantong Ctr Dis Control & Prevent, Nantong 226007, Peoples R China
来源：
CELL DEATH DISCOVERY | 2021年 / 7卷 / 01期
基金：
中国国家自然科学基金;
关键词：
CELL-PROLIFERATION; GASTRIC-CANCER; LUNG-CANCER; JWA; EXPRESSION; GROWTH; RESISTANCE; MIGRATION; INVASION; HER2;
D O I：
10.1038/s41420-021-00426-y
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
The overexpression of HER2 is associated with a malignant proliferation of breast cancer. In this study, we developed a non-cytotoxic JWA gene activating compound 1 (JAC1) to inhibit the proliferation of HER2-positive breast cancer cells in vitro and in vivo experimental models. JAC1 increased the ubiquitination of HER2 at the K716 site through the E3 ubiquitin ligase SMURF1 which was due to the decreased expression of NEDD4, the E3 ubiquitin ligase of SMURF1. In conclusion, JAC1 suppresses the proliferation of HER2-positive breast cancer cells through the JWA triggered HER2 ubiquitination signaling. JAC1 may serve as a potential therapeutic agent for HER2-positive breast cancer.
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页数：13
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