N4BP3 promotes breast cancer metastasis via NEDD4-mediated E-cadherin ubiquitination and degradation. (1st December 2022)

• Record Type: Journal Article
• Authors: Luo, Meng; Li, Jinfan; Yang, Qi; Xu, Song; Zhang, Kun; Chen, Jing; Zhang, Suzhan; Zheng, Shu; Zhou, Jiaojiao
• Is Part Of: Cancer letters. Volume 550(2022)
• Publication Date: 2022-12-01
• Subjects: N4BP3 -- NEDD4 -- E-cadherin -- Breast cancer -- Epithelial-mesenchymal transition; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2022.215926
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: The molecular mechanisms driving metastatic progression in breast cancer patients remain poorly understood. Here, we identified N4BP3 as a new regulator in promoting breast cancer metastasis. N4BP3 is enriched in breast tumor tissue and negatively correlates with clinical outcomes in breast cancer patients. The results show that N4BP3 plays a crucial role in regulating breast cancer cell invasion in vitro, and N4BP3 depletion suppresses metastases formation in vivo . N4BP3 alters the expression of epithelial-mesenchymal transition markers and specifically targets E-cadherin in breast cancer cells. Intriguingly, we identified a novel E3 ligase NEDD4 for E-cadherin, and further revealed that N4BP3 promotes breast cancer metastasis via NEDD4-mediated E-cadherin ubiquitination and degradation. Together, this study uncovers an unprecedented role for N4BP3 in breast cancer metastasis and elucidates the underlying molecular mechanisms. Highlights: N4BP3 has a prognostic value in breast cancer patients. N4BP3 promotes breast cancer cell metastasis. N4BP3 downregulates E-cadherin via NEDD4. NEDD4 is a novel E3 ligase for E-cadherin.