PRAF3 induces apoptosis and inhibits migration and invasion in human esophageal squamous cell carcinoma

Guo-Zhen Shi,Zhi-Jun Ge,Sheng-Dong Huang,Guo-Jun Jiang,Yang Yuan,De-Jun Gong,Jing Tao,Yong-Fei Tan,Jian Zhou

doi:10.1186/1471-2407-12-97

Abstract

BackgroundPrenylated Rab acceptor 1 domain family member 3 (PRAF3) is involved in the regulation of many cellular processes including apoptosis, migration and invasion. This study was conducted to investigate the effect of PRAF3 on apoptosis, migration and invasion in human esophageal squamous cell carcinoma (ESCC).MethodsThe expression of PRAF3 mRNA and protein in primary ESCC and the matched normal tissues (57cases) was determined by quantitative RT-PCR and Western blot. Immunohistochemical analysis of PRAF3 expression was carried out in paraffin-embedded sections of ESCC and correlated with clinical features. The role of PRAF3 in apoptosis, migration and invasion was studied in ESCC cell lines of Eca109 and TE-1 through the adenovirus mediated PRAF3 gene transfer. The effect of PRAF3 on apoptosis was analyzed by annexin V-FITC assay. The regulation of PRAF3 on migration was determined by transwell and wounding healing assay, while the cellular invasion was analyzed by matrigel-coated transwell assay.ResultsWe found that the expression of PRAF3 was significantly down-regulated in ESCC tissue compared with the matched normal tissue and was correlated with the clinical features of pathological grade, tumor stage and lymph node metastasis. Moreover, overexpression of PRAF3 induced cell apoptosis through both caspase-8 and caspase-9 dependent pathways, and inhibited cell migration and invasion by suppressing the activity of both MMP-2 and MMP-9 in human ESCC cell lines.ConclusionsOur data suggest that PRAF3 plays an important role in the regulation of tumor progression and metastasis and serves as a tumor suppressor in human ESCC. We propose that PRAF3 might be used as a potential therapeutic agent for human ESCC.

Highlights

Prenylated Rab acceptor 1 domain family member 3 (PRAF3) is involved in the regulation of many cellular processes including apoptosis, migration and invasion
PRAF3 expression is down-regulated in esophageal squamous cell carcinoma (ESCC) specimens and is correlated with pathological grade, tumor stage and lymph node metastasis In the present study, we evaluated the expression of PRAF3 in ESCC and the matched normal esophageal tissues by immunohistochemical analysis
It was found that PRAF3 was weakly expressed in ESCC tissues, whereas it was moderately expressed in normal esophageal epithelium (Figure 1A)

Summary

Introduction

Prenylated Rab acceptor 1 domain family member 3 (PRAF3) is involved in the regulation of many cellular processes including apoptosis, migration and invasion. This study was conducted to investigate the effect of PRAF3 on apoptosis, migration and invasion in human esophageal squamous cell carcinoma (ESCC). Previous studies reported that PRAF3 is involved in the regulation of intracellular protein transport, DNA damage repair, oxidative stress and other functions, where PRAF3 has been shown to induce cell apoptosis and inhibit cell migration via different pathways [7,8,9,10]. Unlike other members (PRAF1 and PRAF2) of the PRA family which promote tumor cell proliferation and migration and may function as oncogenes [11,12,13], PRAF3 is considered as a tumor suppressor since it could induce cell apoptosis and inhibit metastasis in tumors such as breast cancer, cervical cancer, melanoma and osteosarcoma [7,9,10]. The biological role of PRAF3 in ESCC has not been documented

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Conclusion