NRBPI is downregulated in breast cancer and NRBPI overexpression inhibits cancer cell proliferation through Wnt/β-catenin signaling pathway

Abstract

Nuclear receptor binding protein 1 (NRBP1) is a highly conserved protein that is ubiquitously expressed across cell types in humans. NRBP1 has been recently identified as an adaptor protein. It has been suggested that it plays important roles in cellular homeostasis and the pathophysiology of cancer. To determine whether NRBP1 is involved in the pathophysiology of breast cancer, we performed a correlation study between the expression level of NRBP1 and the clinicopathological features in 92 breast cancer patients. A strong correlation was detected between NRBP1 expression and advanced histopathology grades, tumor, node, and metastasis stage, tumor diameter, lymph node involvement, as well as the recurrence of breast cancer in 92 tested patients. The tumor tissues from patients also expressed lower NRBP1 than did adjacent healthy tissues. Furthermore, we overexpressed NRBP1 in MCF-7 and MDA-MB-231 breast cancer cell lines and found NRBP1 upregulation-inhibited cell proliferation by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Blocking the autocrine Wnt signaling pathway by LGK974 could remove the NRBP1-overexpression-induced inhibition in breast cancer cells. The results of this study suggest that NRBP1 plays a tumor-suppressive role in breast cancer pathophysiology, which likely acts through the Wnt/β-catenin signaling pathway.