Reduced expression of odd-skipped related transcription factor 1 promotes proliferation and invasion of breast cancer cells and indicates poor patient prognosis

Yuan Wang; Lei Lei; Fang Xu; Hong-Tao Xu

doi:10.3892/ol.2020.11820

Reduced expression of odd-skipped related transcription factor 1 promotes proliferation and invasion of breast cancer cells and indicates poor patient prognosis

Oncol Lett. 2020 Sep;20(3):2946-2954. doi: 10.3892/ol.2020.11820. Epub 2020 Jul 7.

Authors

Yuan Wang^{1

2}, Lei Lei², Fang Xu³, Hong-Tao Xu²

Affiliations

¹ Department of Pathology, Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China.
² Department of Pathology, The First Hospital and College of Basic Medical Sciences of China Medical University, Shenyang, Liaoning 110001, P.R. China.
³ Department of Orthopaedics, Jinzhou Second Hospital, Jinzhou, Liaoning 121000, P.R. China.

Abstract

Odd-skipped related transcription factor 1 (OSR1) serves an important role in the development of the intermediate mesoderm; however, its expression in cancer remains unknown. The present study aimed to explore the expression and role of OSR1 in breast cancer development. Immunohistochemistry was performed to detect OSR1 expression in breast cancer tissue and western blot analysis was used to evaluate the expression of OSR1 and related proteins, including β-catenin, c-Myc and cyclin D1. OSR1 expression was increased following transfection of MCF7 cells with OSR1 overexpression vector (MCF7-OSR1) and reduced by transfecting MDA-MB-231 cells with small interfering (si)RNA targeting OSR1 (MDA-MB-231-siOSR1). Cell proliferation and Matrigel™ invasion assays were used to investigate the effects of OSR1 on the proliferation and invasion of breast cancer cells. OSR1 was downregulated in breast cancer tissue compared with that in normal breast tissue and associated with lymph node metastases and estrogen receptor (ER) expression. Furthermore, reduced expression of OSR1 was associated with poor patient prognosis. Overexpression of OSR1 inhibited the proliferation and invasion of breast cancer cells. Western blot analysis of MCF7-OSR1 cells demonstrated that compared with that in the control cells, the expression of E-cadherin was increased, whereas that of key epithelial-mesenchymal transition (EMT) proteins, N-cadherin and Snail, was decreased. In addition, overexpression of OSR1 significantly decreased the expression level of β-catenin and Wnt target genes, such as c-Myc and cyclin D1, compared with that in the control cells. These expression patterns were reversed in the MDA-MB-231-siOSR1 cells. The results of the present study suggested that OSR1 downregulates the activity of the Wnt signaling pathway and EMT, which inhibits the proliferative and invasive abilities of breast cancer cells.

Keywords: Wnt signaling pathway; breast cancer; epithelial-mesenchymal transition process; odd-skipped related transcription factor 1.