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

// Yueyu Cao 1, 3 , Mengdan Wei 2, 3 , Bing Li 2, 3 , Yali Liu 2, 3 , Ying Lu 2, 3 , Zhipeng Tang 1, 3 , Tianbao Lu 3 , Yujiao Yin 1, 3 , Zhiqiang Qin 1, 2, 3, 4 , Zengguang Xu 2, 3 1 Department of Oncology, Shanghai East Hospital, Dalian Medical University, Shanghai 200120, China 2 Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China 3 Research Center for Translational Medicine and Key Laboratory of Arrhythmias, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China 4 Departments of Microbiology/Immunology/Parasitology, Louisiana State University Health Sciences Center, Louisiana Cancer Research Center, New Orleans, LA 70112, USA Correspondence to: Zhiqiang Qin, e-mail: zqin@lsuhsc.edu Zengguang Xu, e-mail: xuzg1998@163.com Keywords: EIF4G1, USP10, NSCLC, lung cancer Received: January 26, 2016      Accepted: March 02, 2016      Published: March 18, 2016 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.