Functional role of eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) in NSCLC.

Yueyu Cao,Yali Liu,Zhipeng Tang,Bing Li,Mengdan Wei,Ying Lu,Tianbao Lu,Yujiao Yin,Zengguang Xu,Zhiqiang Qin

doi:10.18632/oncotarget.8168

Abstract

Eukaryotic translation initiation factor 4 gamma 1(EIF4G1) is related to tumorigenesis and tumor progression. However, its role and the underlying mechanisms in the regulation of tumor development in non–small cell lung cancers (NSCLC) remain largely unknown. Here we report that the levels of EIF4G1 expression are much higher in NSCLC cell lines and tumor tissues than those in the normal lung cells and adjacent normal tissues from the same patients. Using shRNA to knock down EIF4G1 expression stably, we found EIF4G1 required for NSCLC cell proliferation, anchorage-independent growth, migration and invasion. Furthermore, silencing of EIF4G1 induces NSCLC cell apoptosis and causes G0/G1 cell cycle arrest. To identify the partner protein network of EIF4G1 in NSCLC cells, we found that Ubiquitin-specific protease 10 (USP10) can directly interacts with EIF4G1, while acting as a negative regulator for EIF4G1-mediated functions. Together, our results indicate that EIF4G1 functions as an oncoprotein during NSCLC development, which may represent a novel and promising therapeutic target in lung cancer.

Highlights

Lung cancer is a common malignant disease and the leading cause of cancer-related death in the world [1], which falls into the broad categories of non– small cell lung cancers (NSCLC, encompassing lung adenocarcinomas, squamous cell lung carcinomas and large cell carcinomas [2]) and SCLC [3]
We found that eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) is required for non–small cell lung cancers (NSCLC) cell survival and proliferation, and it acts as an oncoprotein to promote lung cancer cell malignant behaviors
We found that EIF4G1 expression was greatly increased in 3 NSCLC cell lines (H460, A549, H1299) when compared to normal human bronchial epithelial cell line, 16HBE (Figure 1A)

Summary

Introduction

Lung cancer is a common malignant disease and the leading cause of cancer-related death in the world [1], which falls into the broad categories of non– small cell lung cancers (NSCLC, encompassing lung adenocarcinomas, squamous cell lung carcinomas and large cell carcinomas [2]) and SCLC [3]. Better understanding of the molecular biology of NSCLC has led to a revolution in the treatment of these neoplasms [8]. The identification of oncogenic activation of particular tyrosine kinases (TKs) in some patients with advanced NSCLC in particular those mutations in epidermal growth factor receptor (EGFR) [10,11,12] have demonstrated that detection of such mutations in the plasma of newly diagnosed NSCLC patients is feasible [13], and led to the development of personalized medicine for these patients. There is an urgent need for further understanding the molecular mechanisms of lung cancer tumorigenesis and identifying new therapeutic targets to improve the prognosis of cancer patients [15]

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Conclusion