N4BP3 promotes breast cancer metastasis via NEDD4-mediated E-cadherin ubiquitination and degradation

被引：13
|
作者：
Luo, Meng [1 ,2 ]
Li, Jinfan [3 ]
Yang, Qi
Xu, Song [4 ]
Zhang, Kun [1 ]
Chen, Jing
Zhang, Suzhan [1 ]
Zheng, Shu [1 ]
Zhou, Jiaojiao [1 ,3 ,5 ,6 ]
机构：
[1] Zhejiang Univ, Affiliated Hosp 2, Dept Breast Surg & Oncol, Sch Med, Hangzhou 310009, Peoples R China
[2] Zhejiang Univ, Key Lab Canc Prevent & Intervent, China Natl Minist Educ, Sch Med, Hangzhou 310009, Peoples R China
[3] Zhejiang Univ, Affiliated Hosp 2, Dept Pathol, Sch Med, Hangzhou 310009, Peoples R China
[4] Zhejiang Univ, Lab Gastroenterol Dept, Affiliated Hosp 2, Sch Med, Hangzhou 310009, Peoples R China
[5] Zhejiang Univ, Canc Ctr, Hangzhou 310009, Peoples R China
[6] Zhejiang Univ, Affiliated Hosp 2, Dept Breast Surg & Oncol, Coll Med, 88 Jie Fang Rd, Hangzhou 310009, Zhejiang, Peoples R China
来源：
CANCER LETTERS | 2022年 / 550卷
关键词：
N4BP3; NEDD4; E-cadherin; Breast cancer; Epithelial-mesenchymal transition; EPITHELIAL-MESENCHYMAL TRANSITION; CELL-ADHESION; PROTEIN; EXPRESSION; ENDOCYTOSIS; RECEPTOR; FAMILY; HAKAI;
D O I：
10.1016/j.canlet.2022.215926
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
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.
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页数：13
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