The E3 ubiquitin ligase Cbl-b inhibits tumor growth in multidrug-resistant gastric and breast cancer cells

被引：14
|
作者：
Che, X. [1 ,2 ]
Zhang, Y. [1 ,2 ]
Qu, X. [1 ,2 ]
Guo, T. [1 ,2 ]
Ma, Y. [1 ,2 ]
Li, C. [1 ,2 ]
Fan, Y. [1 ,2 ]
Hou, K. [1 ,2 ]
Cai, Y. [1 ,2 ]
Yu, R. [1 ,2 ]
Zhou, H. [1 ,2 ]
He, X. [1 ,2 ]
Wu, H. [1 ,2 ]
Liu, Y. [1 ,2 ]
Xu, L. [1 ,2 ]
机构：
[1] China Med Univ, Hosp 1, Dept Med Oncol, Shenyang 110001, Liaoning, Peoples R China
[2] China Med Univ, Hosp 1, Key Lab Anticanc Drugs & Biotherapy Liaoning Prov, Shenyang 110001, Liaoning, Peoples R China
来源：
NEOPLASMA | 2017年 / 64卷 / 06期
关键词：
Cbl-b; IGF-1R; MDR; proliferation; TYROSINE KINASE INHIBITORS; C-CBL; INDUCED APOPTOSIS; RECEPTOR; EGFR;
D O I：
10.4149/neo_2017_610
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Most receptor tyrosine kinases (RTKs) contribute to tumor growth, and their ubiquitination and degradation is related to the inhibition of tumor growth. Our previous study showed that the ubiquitin ligase Cbl-b was expressed at low levels in multidrug-resistant (MDR) gastric cancer cells compared with their parental cells. However, whether enhancement of Cbl-b expression in MDR cancer cells could prevent tumor proliferation via ubiquitination and degradation of RTK remains unclear. In the present study, Cbl-b overexpression reduced cell proliferation in MDR gastric and breast cancer cells, and effectively inhibited tumor growth in vivo. Additionally, Cbl-b overexpression reduced the total protein level of insulin-like growth factor 1 (IGF-1R), an important member of the RTK family. Moreover, Cbl-b overexpression promoted interaction of Cbl-b with IGF-1R, and induced ubiquitination and degradation of IGF-1R and inactivation of the IGF-1R pathway. These results suggest that the ubiquitin ligase Cbl-b inhibited tumor growth via ubiquitination and degradation of IGF-1R in MDR gastric and breast cancer cells.
引用
收藏
页码：887 / 892
页数：6
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