The metastatic suppressor NDRG1 inhibits EMT, migration and invasion through interaction and promotion of caveolin-1 ubiquitylation in human colorectal cancer cells

被引：72
作者：
Mi, L. [1 ,2 ,3 ,4 ]
Zhu, F. [1 ,2 ]
Yang, X. [1 ,2 ]
Lu, J. [1 ,2 ]
Zheng, Y. [5 ]
Zhao, Q. [5 ]
Wen, X. [4 ]
Lu, A. [1 ,2 ]
Wang, M. [1 ,2 ]
Zheng, M. [1 ,2 ]
Ji, J. [3 ,4 ]
Sun, J. [1 ,2 ]
机构：
[1] Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Gen Surg, Shanghai 200025, Peoples R China
[2] Shanghai Minimally Invas Surg Ctr, Shanghai, Peoples R China
[3] Peking Univ, Canc Hosp & Inst, Dept Gastrointestinal Surg, Beijing, Peoples R China
[4] Peking Univ, Canc Hosp & Inst, Div Gastrointestinal Canc Translat Res Lab, Key Lab Carcinogenesis & Translat Res,Minist Educ, Beijing, Peoples R China
[5] Shanghai Jiao Tong Univ, Sch Med, Dept Pathophysiol, Key Lab Cell Differentiat & Apoptosis,Minist Educ, Shanghai, Peoples R China
来源：
ONCOGENE | 2017年 / 36卷 / 30期
基金：
中国国家自然科学基金;
关键词：
EPITHELIAL-MESENCHYMAL TRANSITION; RNA-POLYMERASE-II; PROSTATE-CANCER; PROTEASOMAL DEGRADATION; INDUCED UBIQUITINATION; ELEVATED EXPRESSION; LUNG ADENOCARCINOMA; SIGNALING PATHWAYS; GENE-EXPRESSION; DOWN-REGULATION;
D O I：
10.1038/onc.2017.74
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
N-myc downstream-regulated gene 1 (NDRG1) has been reported to act as a key regulatory molecule in tumor progression-related signaling pathways, especially in tumor metastasis. However, the related mechanism has not been fully discovered yet. Herein we demonstrated that the novel molecule of cell migration and invasion, caveolin-1, has direct interaction with NDRG1 in human colorectal cancer (CRC) cells. Moreover, we discovered that NDRG1 reduces caveolin-1 protein expression through promoting its ubiquitylation and subsequent degradation via the proteasome in CRC cells. In addition, caveolin-1 mediates the suppressive function of NDRG1 in epithelial-mesenchymal transition, migration and invasion in vitro and metastasis in vivo. These results help to fulfill the potential mechanisms of NDRG1 in anti-metastatic treatment for human colorectal cancer.
引用
收藏
页码：4323 / 4335
页数：13
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