SGEF is a potential prognostic and therapeutic target for lung adenocarcinoma

Qian Chen,Quan-Xing Liu,Yuan Qiu,Ji-Gang Dai,Xiao Lu,Hong Zheng,Dong Zhou

doi:10.1186/s12957-018-1331-8

Qian Chen, Quan-Xing Liu + Show 5 more

Open Access

https://doi.org/10.1186/s12957-018-1331-8

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Abstract

BackgroundSH3-containing guanine nucleotide exchange factor (SGEF), a RhoG-specific guanine nucleotide exchange factor (GEF), was consider as a key signal that determines cancer cell invasion. Although SGEF has been considered to highly express in glioma and prostate cancer. However, it is not well illustrated in LAC.MethodsIn this experiment, expression of SGEF was detected in 92 LAC and corresponding normal tissue samples by immunohistochemistry. In addition, we evaluated the invasion and migration of lung adenocarcinoma cells by the gain and loss of SGEF expression. Furthermore, RhoG activity was measured by GST pull-down assay.ResultsSGEF is highly expressed in LAC tissues than in normal lung tissues and was associated with the TNM stage. Lung adenocarcinoma patients with low SGEF subgroup had longer overall survival compared to those with high expression. Furthermore, univariate analysis showed that SGEF expression was an independent prognostic factor for overall survival in lung adenocarcinoma. Silencing of SGEF effectively suppressed the invasion and migration of human lung adenocarcinoma cells in vitro by inhibiting RhoG activity, and over-expression of SGEF could reverse this phenomena.ConclusionSGEF is a novel prognostic target in human lung adenocarcinoma.

Highlights

Src homology 3 (SH3)-containing guanine nucleotide exchange factor (SGEF), a RhoG-specific guanine nucleotide exchange factor (GEF), was consider as a key signal that determines cancer cell invasion
We found that SH3-containing guanine nucleotide exchange factor (SGEF) was mostly localized in the cell cytoplasm, and the proportion of cells with high SGEF expression was significantly higher in the lung adenocarcinoma tissues (58.7%, 54/92) than in the adjacent normal tissues (17.24%, 15/87) (Fig. 1d and Table 1)
High SGEF is closely related with advanced TNM stage and poor prognosis in lung adenocarcinoma (LAC) We investigated the potential relationship of SGEF expression and clinical pathological parameters

Summary

Introduction

SH3-containing guanine nucleotide exchange factor (SGEF), a RhoG-specific guanine nucleotide exchange factor (GEF), was consider as a key signal that determines cancer cell invasion. SGEF has been considered to highly express in glioma and prostate cancer. It is not well illustrated in LAC. SGEF is a RhoG-specific guanine nucleotide exchange factor (GEF) [6]. The domains of DH/PH in SGEF strongly exchange RhoG [8] and interact with HPV E6 oncoprotein which contains PDZ domain, accelerating invasive phenotype of the HPV-induced cervical cancer. EGFR stability was meditated by SGEF through inhibited EGFR trafficking promoting prostate cancer cell progression. There is no information about the functional and clinical value of SGEF in LAC. It deserves to explore the SGEF expression and function in LAC

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Results

Conclusion