title: Overexpression of Oct4 suppresses the metastatic potential of breast cancer cells via Rnd1 downregulation.
abstract: Although Oct4 is known as a critical transcription factor involved in maintaining "stemness", its role in tumor metastasis is still controversial. Herein, we overexpressed and silenced Oct4 expression in two breast cancer cell lines, MDA-MB-231 and 4T1, separately. Our data showed that ectopic overexpression of Oct4 suppressed cell migration and invasion in vitro and the formation of metastatic lung nodules in vivo. Conversely, Oct4 downregulation increased the metastatic potential of breast cancer cells both in vitro and in vivo. Furthermore, we identified Rnd1 as the downstream target of Oct4 by ribonucleic acid sequencing (RNA-seq) analysis, which was significantly downregulated upon Oct4 overexpression. Chromatin immunoprecipitation assays revealed the binding of Oct4 to the promoter region of Rnd1 by ectopic overexpression of Oct4. Dual luciferase assays indicated that Oct4 overexpression suppressed transcriptional activity of the Rnd1 promoter. Moreover, overexpression of Rnd1 partially rescued the inhibitory effects of Oct4 on the migration and invasion of breast cancer cells. Overexpression of Rnd1 counteracted the influence of Oct4 on the formation of cell adhesion and lamellipodia, which implied a potential underlying mechanism involving Rnd1. In addition, we also found that overexpression of Oct4 led to an elevation of E-cadherin expression, even in 4T1 cells that possess a relatively high basal level of E-cadherin. Rnd1 overexpression impaired the promoting effects of Oct4 on E-cadherin expression in MDA-MB-231 cells. These results suggest that Oct4 affects the metastatic potential of breast cancer cells through Rnd1-mediated effects that influence cell motility and E-cadherin expression.
authors: Department of Pathology, Medical School of Nankai University, Tianjin 300071, China.
authors: Long
authors: L
authors: Shen
authors: Department of Immunology, Medical School of Nankai University, Tianjin 300071, China.
authors: Kunhua
authors: K
authors: Qin
authors: Department of Pathology, Medical School of Nankai University, Tianjin 300071, China.
authors: Dekun
authors: D
authors: Wang
authors: Department of Immunology, Medical School of Nankai University, Tianjin 300071, China.
authors: Yan
authors: Y
authors: Zhang
authors: Department of Immunology, Medical School of Nankai University, Tianjin 300071, China.
authors: Nan
authors: N
authors: Bai
authors: West China Hospital, Molecular Medicine Research Centre, State Key Lab Biotherapy, Sichuan University, Chengdu 610064, China.
authors: Shengyong
authors: S
authors: Yang
authors: Department of Immunology, Beijing Union Medical School, Beijing 100010, China.
authors: Yunping
authors: Y
authors: Luo
authors: Department of Immunology, Medical School of Nankai University, Tianjin 300071, China.
authors: Rong
authors: R
authors: Xiang
authors: Department of Pathology, Medical School of Nankai University, Tianjin 300071, China. Electronic address: xiaoyuetan@nankai.edu.cn.
authors: Xiaoyue
authors: X
authors: Tan
keywords: Breast cancer; E-cadherin; Metastasis; Oct4; Rnd1