HRD1 suppresses the growth and metastasis of breast cancer cells by promoting IGF-1R degradation.
HRD1 suppresses the growth and metastasis of breast cancer cells by promoting IGF-1R degradation.
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HRD1通过促进IGF-1R降解抑制乳腺癌细胞的生长和转移
DOI：
10.18632/oncotarget.5733
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发表时间：
2015-12-15
期刊：
影响因子：
--
通讯作者：
Su DM
中科院分区：
文献类型：
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作者：
Xu YM;Wang HJ;Chen F;Guo WH;Wang YY;Li HY;Tang JH;Ding Y;Shen YC;Li M;Xuan WY;Liu LH;Wang J;Wang XR;Gao ZJ;Liang XB;Su DM
HRD 1（3-羟基-3-甲基戊二酰还原酶降解）是一种E3泛素连接酶。我们发现HRD 1在170例乳腺癌组织中显著下调。HRD 1低表达与乳腺癌患者的临床病理特征和较短的生存期相关。P65特异性结合HRD 1启动子并抑制HRD 1表达。抑制NF-κB活性可逆转IL-6诱导的HRD 1表达下调。HRD 1与IGF-1 R相互作用并促进其泛素化和蛋白酶体降解。HRD 1的过表达可抑制乳腺癌细胞的生长、迁移和侵袭。此外，HRD 1减弱了IL-6诱导的MCF 10A细胞中的上皮-间质转化。这些发现揭示了HRD 1在乳腺癌中的新作用。
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-κB 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.