HRD1 suppresses the growth and metastasis of breast cancer cells by promoting IGF-1R degradation

被引：34

作者：

Xu, Yue-Mei ^{[1
]}

Wang, Hong-Jiang ^{[2
]}

Chen, Fang ^{[3
]}

Guo, Wan-Hua ^{[4
]}

Wang, Yan-Yang ^{[4
]}

Li, Hang-Yu ^{[5
]}

Tang, Jin-Hai ^{[6
]}

Ding, Ying ^{[1
]}

Shen, Ya-Chen ^{[7
]}

Li, Min ^{[1
,7
]}

Xuan, Wen-Ying ^{[1
]}

Liu, Lin-Hui ^{[1
]}

Wang, Jia ^{[2
]}

Wang, Xue-Rong ^{[1
]}

Gao, Ze-Jun ^{[1
]}

Liang, Xiu-Bin ^{[7
]}

Su, Dong-Ming ^{[1
,7
,8
]}

机构：

[1] Nanjing Med Univ, Dept Pathol, State Key Lab Reprod Med, Nanjing, Jiangsu, Peoples R China

[2] Dalian Med Univ, Affiliated Hosp 1, Dept Breast Surg, Dalian, Peoples R China

[3] Nanjing Med Univ, Key Lab Human Funct Genom Jiangsu Prov, Nanjing, Jiangsu, Peoples R China

[4] Nanjing Univ, Affiliated Drum Tower Hosp, Dept Nucl Med, Nanjing 210008, Jiangsu, Peoples R China

[5] China Med Univ, Affiliated Hosp 4, Dept Gen Surg, Shenyang 110001, Peoples R China

[6] Nanjing Med Univ, Affiliated Jiangsu Canc Hosp, Dept Gen Surg, Nanjing, Jiangsu, Peoples R China

[7] Nanjing Med Univ, Ctr Metab Res, Nanjing, Jiangsu, Peoples R China

[8] Nanjing Med Univ, Affiliated Hosp 2, Ctr Cellular therapy, Nanjing, Jiangsu, Peoples R China

来源：

ONCOTARGET | 2015年 / 6卷 / 40期

基金：

中国国家自然科学基金;

关键词：

HRD1; breast cancer; metastasis; IGF-1R; degradation; EPITHELIAL-MESENCHYMAL TRANSITION; FACTOR-I RECEPTOR; TUMOR ANGIOGENESIS; GASTRIC-CANCER; SYNOVIOLIN; EXPRESSION; PROTEIN; EMT; ASSOCIATION; PLASTICITY;

D O I：

10.18632/oncotarget.5733

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

HRD1 (3-hydroxy-3-methylglutaryl reductase degradation) is an E3 ubiquitin ligase. We found that HRD1 was significantly downregulated in 170 breast cancer tissues. Low tumoral HRD1 expression was correlated with clinicopathological characteristics and a shorter survival in breast cancer patients. P65 specifically bound to the HRD1 promoter and inhibited HRD1 expression. Suppression of NF-kappa B activity reversed IL-6-induced downregulation of HRD1 expression. HRD1 interacted with IGF-1R and promoted its ubiquitination and degradation by the proteasome. Overexpression of HRD1 resulted in the inhibition of growth, migration and invasion of breast cancer cells in vitro and in vivo. Furthermore, HRD1 attenuated IL-6-induced epithelial-mesenchymal transition in MCF10A cells. These findings uncover a novel role for HRD1 in breast cancer.

引用

页码：42854 / 42867

页数：14

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