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

• DOI: 10.1038/s41420-021-00426-y
• Publication Date: 2021-04-19T08:07:37Z
• Authors: Yanlin Ren; Dongyin Chen; Zurong Zhai; Junjie Chen; Aiping Li; Yan Liang; Jianwei Zhou
• Keywords: 0301 basic medicine; 03 medical and health sciences; QH573-671; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; Cytology; RC254-282; Article; 3. Good health

AbstractThe 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.