HRD1 Inhibits The Growth And Metastasis Of Breast Cancer By Affecting IGF-1R Degradation

Breast cancer is one of the major diseases that threaten human health.In-depth understanding of the molecular mechanisms involved in the development of breast cancer has been the focus of medical research.E3 ubiquitin ligase degrades intracellular protein for participating important physiological and pathological processes involved in the body.In recent years,studies have shown that many diseases including malignant tumors,with different E3 ubiquitin ligase expression and function related.HRD1,an E3 ubiquitin ligase,locates in Endoplasmic reticulum membrane,is implicated in the regulation of embryogenesis and rheumatoid arthritis,but its role in breast cancer is unclear.The purpose of this study was to explore the biological function and clinical significance of HRD1 in breast cancer.IGF-1R activity has a positive regulatory role in tumor cell's malignant transformation.IGFs combined with IGF-1R,promote cell proliferation and malignant transformation in early tumorigenesis.As for the malignant transformation of the tumor cells have been issued,it maintains the growth of malignant cells;promote the transfer of the effect of IGFs combined with IGF-1R.Compared with the corresponding adjacent tissues,high expression of IGF-1R is one of the main features of the vast majority of primary breast cancer cells.In the previous study of this subject,we found that the expression of HRD1 was evaluated using Western blot,immunohistochemical staining and tissue microarray.The effects of HRD1 on growth and metastasis of breast cancer was studied in vitro and in vivo.HRD1 was downregulated in breast cancer when compared to non-cancer tissues.Downregulation of HRD1 expression was correlated with clinicopathological characteristics and a shorter survival in breast cancer patients.HRD1 also interacted with IGF-1R and promoted its ubiquitination and degradation by the proteasome.Overexpression of HRD1 inhibited growth,migration and invasion of breast cancer cells in vitro and in vivo.HRD1 was also involved in the epithelial-mesenchymal transition(EMT).Decreased HRD1 expression in breast cancer cells resulted in increased growth and metastasis of breast cancer and contributed to poor overall survival of breast cancer patients.HRD1 expression therefore represents a potential treatment target for breast cancer.