Open AccessThe E3 ubiquitin ligase Cbl-b inhibits tumor growth in multidrug-resistant gastric and breast cancer cells
Author(s) -
Xiangyu Che,
Y Zhang,
Xiujuan Qu,
Tao Guo,
Yanju Ma,
C Li,
Yibo Fan,
Kezuo Hou,
Yingchun Cai,
Rong Yu,
Hongxing Zhang,
Xialian He,
Hao Wu,
Yunpeng Liu,
Linying Xu
Publication year - 2017
Publication title -
neoplasma
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.628
H-Index - 50
eISSN - 1338-4317
pISSN - 0028-2685
DOI - 10.4149/neo_2017_610
Subject(s) - ubiquitin ligase , ubiquitin , cancer research , cell growth , cancer , receptor tyrosine kinase , chemistry , cancer cell , biology , microbiology and biotechnology , signal transduction , biochemistry , genetics , gene
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.