Derlin-1 functions as a growth promoter in breast cancer

• Published in: Biological chemistry Vol. 401; no. 3; pp. 377 - 387
• Main Authors: Liu, Yansong, Wang, Ziming, Liu, Handong, Wang, Xin, Zhang, Zhonghua, Xiao, Bin, An, Baoming, Zhang, Jun
• Format: Journal Article
• Language: English
• Published: Germany De Gruyter 01.03.2020; Walter de Gruyter GmbH
• Subjects: AKT; AKT protein; Apoptosis; BAX protein; Breast cancer; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell Proliferation; Cyclin D1; Derlin-1; Female; Gene expression; Humans; Immunohistochemistry; Membrane Proteins - genetics; Membrane Proteins - metabolism; Phenotypes; prognosis; Signal transduction; siRNA; Tumor Cells, Cultured; Tumors; breast cancer; AKT; Derlin-1; prognosis
• ISSN: 1431-6730; 1437-4315
• DOI: 10.1515/hsz-2018-0442

Breast cancer is one of the most common malignant tumors in women. Derlin-1 has been found to be overexpressed in several human cancers in addition to playing an important role in tumor processes; however, the expression patterns and functions of Derlin-1 in human breast cancer are not fully understood. In this study, we found that Derlin-1 overexpression was higher in breast cancer compared to normal samples through TCGA and GTEx database analyses. Kaplan-Meier plotter analysis showed that Derlin-1 was a predicting factor for patient prognosis. Derlin-1 expression was significantly up-regulated in breast cancer tissues (18/30, 60.00%) compared to corresponding paracancerous tissue (9/30, 30.00%,  < 0.05) as detected by immunohistochemistry, and the expression of Derlin-1 was correlated to pathological grading. siRNA interference of Derlin-1 inhibited cell proliferation, which is associated with the promotion of apoptosis and migration. Derlin-1 knockdown suppressed the protein levels of p-AKT and Cyclin D1 while up-regulating Caspase3 and Bax. GEPIA database analysis showed that and were downstream target genes, and the expression of and was suppressed in Derlin-1 knockdown cells. Taken together, our results demonstrated that Derlin-1 is overexpressed in breast cancer and promoted a malignant phenotype through the AKT signaling pathway.