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

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 u...

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Detalles Bibliográficos
Autores principales: Ren, Yanlin, Chen, Dongyin, Zhai, Zurong, Chen, Junjie, Li, Aiping, Liang, Yan, Zhou, Jianwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055679/
https://www.ncbi.nlm.nih.gov/pubmed/33875644
http://dx.doi.org/10.1038/s41420-021-00426-y
Descripción
Sumario: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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