JAC1通过JWA/p38/SMURF1/HER2信号通路抑制乳腺癌的增殖。
JAC1 suppresses proliferation of breast cancer through the JWA/p38/SMURF1/HER2 signaling.
作者信息
Ren Yanlin, Chen Dongyin, Zhai Zurong, Chen Junjie, Li Aiping, Liang Yan, Zhou Jianwei
机构信息
Department of Molecular Cell Biology & Toxicology, Center for Global Health, School of Public Health, Nanjing Medical University, 211166, Nanjing, China.
Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, 211166, Nanjing, China.
出版信息
Cell Death Discov. 2021 Apr 19;7(1):85. doi: 10.1038/s41420-021-00426-y.
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.
HER2的过表达与乳腺癌的恶性增殖相关。在本研究中，我们开发了一种无细胞毒性的JWA基因激活化合物1（JAC1），以在体外和体内实验模型中抑制HER2阳性乳腺癌细胞的增殖。JAC1通过E3泛素连接酶SMURF1增加了HER2在K716位点的泛素化，这是由于SMURF1的E3泛素连接酶NEDD4的表达降低所致。总之，JAC1通过JWA触发的HER2泛素化信号传导抑制HER2阳性乳腺癌细胞的增殖。JAC1可能作为HER2阳性乳腺癌的潜在治疗药物。
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