RABEX-5 plays an oncogenic role in breast cancer by activating MMP-9 pathway

Xiang Zhang,Hongyuan Li,Hongzhong Li,Peng Mu,Xinjie Liang,Qiang Liu,Yingjian Wang,Jie Min,Yan Li

doi:10.1186/1756-9966-32-52

Abstract

BackgroundRABEX-5, a guanine nucleotide exchange factor (GEF) for RAB-5, plays an important role in cell mobility and altered expression associated with tumor metastasis. This study aimed to investigate the role of RABEX-5 in proliferation and metastasis of breast cancer in vitro and ex vivo.MethodsRABEX-5 expression was examined in breast cancer, benign tumor and normal breast tissues by immunohistochemistry and western blot. Two stable cell lines were established, the MCF-7/NC negative control cell line and the MCF-7/KD cell line, which stably expressed an RNA interference (RNAi) construct that induced downregulation of RABEX-5 expression. These cell lines were utilized to evaluate the role of RABEX-5 in cell proliferation and migration in vitro and tumorigenicity in vivo. The possible role of RABEX-5 in the regulation of matrix metallopeptidase 9 (MMP-9) was evaluated using western blot and real-time PCR.ResultsRABEX-5 expression was found to be significantly higher in breast cancer tissues compared with benign tumor and normal breast tissues. High levels of RABEX-5 expression were associated with axillary lymph node metastasis. In addition, RABEX-5 silencing significantly reduced cancer cell proliferation, colony formation and migration ability in vitro and inhibited tumor growth in vivo. RABEX −5 knockdown also attenuated the migration of breast cancer cells via modulation of MMP-9 transcriptional activity.ConclusionsOur results indicate that RABEX-5 plays an oncogenic role in breast cancer by modulating the proliferation and metastasis potential of breast cancer cells. Thus, RABEX-5 is a promising prognostic indicator for patients with breast cancer.

Highlights

Expression of A guanine nucleotide exchange factor for RAB-5 (RABEX-5) in tissues and breast cancer cell lines We first examined the expression of RABEX-5 using IHC in breast cancer, benign breast tumor and normal breast tissues
Our results showed that the RABEX-5 expression in breast cancer tissues was significantly higher than that in the benign breast tumor tissues and normal breast tissues (Figure 1A)
The expression level of RABEX-5 was analyzed in 5 breast cancer cell lines (MCF-7, MDA-MB-231, BT549, T47D, and SKBR3)

Summary

Introduction

It has become the most frequently diagnosed cancer and the leading cause of cancer death in females worldwide, with rapidly increasing incidence and mortality rates. Recent clinical data have emerged demonstrating that Ras family genes play important roles in human tumorigenesis. The Ras superfamily of small guanosine triphosphatases (GTPases) contains over 150 human members, with the Ras oncogene proteins as the founding members of this family, which is divided into five major branches on the basis of sequence and functional similarities: Ras, Rho, Rab, Ran and Arf. RABEX-5, a guanine nucleotide exchange factor (GEF) for RAB-5, plays an important role in cell mobility and altered expression associated with tumor metastasis. This study aimed to investigate the role of RABEX-5 in proliferation and metastasis of breast cancer in vitro and ex vivo

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Conclusion