title: HRD1 suppresses the growth and metastasis of breast cancer cells by promoting IGF-1R degradation.
abstract: 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.
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Pathology, Nanjing Medical University, Nanjing, China.
authors.forename: Yue-Mei
authors.initials: YM
authors.lastname: Xu
authors.affiliation: Department of Breast Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, China.
authors.forename: Hong-Jiang
authors.initials: HJ
authors.lastname: Wang
authors.affiliation: Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Nuclear Medicine, The Affiliated Drum Tower Hospital of Nanjing University, Nanjing, China.
authors.forename: Wan-Hua
authors.initials: WH
authors.lastname: Guo
authors.affiliation: Department of Nuclear Medicine, The Affiliated Drum Tower Hospital of Nanjing University, Nanjing, China.
authors.forename: Yan-Yang
authors.initials: YY
authors.lastname: Wang
authors.affiliation: Department of General Surgery, 4th Affiliated Hospital, China Medical University, Shenyang, China.
authors.forename: Hang-Yu
authors.initials: HY
authors.lastname: Li
authors.affiliation: Department of General Surgery, The Affiliated Jiangsu Cancer Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Jin-Hai
authors.initials: JH
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Pathology, Nanjing Medical University, Nanjing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Center of Metabolic Research, Nanjing Medical University, Nanjing, China.
authors.forename: Ya-Chen
authors.initials: YC
authors.lastname: Shen
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Pathology, Nanjing Medical University, Nanjing, China.|Center of Metabolic Research, Nanjing Medical University, Nanjing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Pathology, Nanjing Medical University, Nanjing, China.
authors.forename: Wen-Ying
authors.initials: WY
authors.lastname: Xuan
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Pathology, Nanjing Medical University, Nanjing, China.
authors.forename: Lin-Hui
authors.initials: LH
authors.lastname: Liu
authors.affiliation: Department of Breast Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Pathology, Nanjing Medical University, Nanjing, China.
authors.forename: Xue-Rong
authors.initials: XR
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Pathology, Nanjing Medical University, Nanjing, China.
authors.forename: Ze-Jun
authors.initials: ZJ
authors.lastname: Gao
authors.affiliation: Center of Metabolic Research, Nanjing Medical University, Nanjing, China.
authors.forename: Xiu-Bin
authors.initials: XB
authors.lastname: Liang
authors.affiliation: State Key Laboratory of Reproductive Medicine, Department of Pathology, Nanjing Medical University, Nanjing, China.|Center of Metabolic Research, Nanjing Medical University, Nanjing, China.|Center of Cellular therapy, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Dong-Ming
authors.initials: DM
authors.lastname: Su
mesh_terms: D000368:Aged; D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D047369:Chromatin Immunoprecipitation; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D046888:Tissue Array Analysis; D014162:Transfection; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; C482345:SYVN1 protein, human; D044767:Ubiquitin-Protein Ligases; D017526:Receptor, IGF Type 1
keywords: HRD1; IGF-1R; breast cancer; degradation; metastasis