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.

Correlation of TERT and Stem Cell Markers in the Context of Human Breast Cancer

“…Prominent among these is POU5F1 (better known as OCT4), which has been identified as an essential transcription factor mediating stem-ness. Shen and colleagues studied the effects of overexpression of POU5F1 in MDA-MB-231 and 4T1 breast cancer cell lines, and found that the overexpression of POU5F1 suppressed migration and invasion in these usually aggressive cell types (20).…”

Transcription factor Oct4 promotes osteosarcoma by regulating lncRNA AK055347

“…Notably, a controversial effect of Oct4 was observed in breast cancer. Oct4 was determined to exert a suppressive effect on cell migration and invasion in vitro and the formation of metastatic lung nodules in vivo (28).…”

Curcumin induces apoptotic cell death via Oct4 inhibition and GSK‐3β activation in NCCIT cells

“…In addition, Oct4 directly regulates CCND1 to promote cell cycle progression and accelerate proliferation and invasion of esophageal carcinoma were provided in previous report [36]. In contrast, other reports have found that downregulation of Oct4 in breast cancer cell lines induce epithelial-tomesenchymal transition (EMT) and lead to increased migration, invasion and metastasis to the lung by regulating Rnd1 [37,38]. These contradictory results suggest that different expression levels of Oct4 impart different oncogenic abilities according to state of cancer progression.…”