Journal Article

eIF 2 β, a subunit of translation‐initiation factor EIF 2, is a potential therapeutic target for non‐small cell lung cancer

Sato, Mitsuo, Miyazawa, Ayako, Coombes, Kevin R., Morise, Masahiro, Minna, John D., Goto, Daiki, Kakumu, Tomohiko, Kato, Toshio, Heymach, John V., Hasegawa, Yoshinori, Kondo, Masashi, Byers, Lauren A., Sekido, Yoshitaka, Girard, Luc, Yogo, Naoyuki, Hase, Tetsunari, Tanaka, Ichidai

2018

Overview

To identify novel therapeutic targets for non‐small cell lung cancer ( NSCLC ), we conducted an integrative study in the following 3 stages: (i) identification of potential target gene(s) through sh RNA functional screens in 2 independent NSCLC cell lines; (ii) validation of the clinical relevance of identified gene(s) using public databases; and (iii) investigation of therapeutic potential of targeting the identified gene(s) in vitro. A semi‐genome‐wide sh RNA screen was performed in NCI ‐H358 cells, and was integrated with data from our previous screen in NCI ‐H460 cells. Among genes identified in sh RNA screens, 24 were present in both NCI ‐H358 and NCI ‐H460 cells and were considered potential targets. Among the genes, we focused on eIF 2β, which is a subunit of heterotrimeric G protein EIF 2 and functions as a transcription initiation factor. The eIF 2β protein is highly expressed in lung cancer cell lines compared with normal bronchial epithelial cells, and gene copy number analyses revealed that eIF 2 β is amplified in a subset of NSCLC cell lines. Gene expression analysis using The Cancer Genome Atlas ( TCGA ) dataset revealed that eIF 2 β expression is significantly upregulated in lung cancer tissues compared with corresponding normal lung tissues. Furthermore, high eIF 2 β expression was correlated with poor survival in patients with lung adenocarcinoma, as shown in other cohorts using publicly available online tools. RNA i‐mediated depletion of eIF 2 β suppresses growth of lung cancer cells independently of p53 mutation status, in part through G1 cell cycle arrest. Our data suggest that eIF 2 β is a therapeutic target for lung cancer.

• Publisher: John Wiley & Sons, Inc
• Subject: Adenocarcinoma / Cell cycle / Cell growth / Copy number / Epidermal growth factor / Epithelial cells / Gene expression / Genomes / Lung cancer / Medical prognosis / Non-small cell lung carcinoma / p53 Protein / Phosphorylation / Proteins / RNA-mediated interference / Therapeutic applications / Tumor cell lines / Tumors