Abstract 4384: Role of EIF4G1 in non-small cell lung cancer pathogenesis and targeted therapy

Abstract

Abstract Non-small cell lung cancer (NSCLC) accounts for about 85-90% of lung cancer cases, which represents the number one killer among cancers in US. The majority of lung cancer patients doesn't respond well to conventional chemo-/radio-therapeutic regimens and have a dismal 5-year survival rate of ~15%. The recent introduction of targeted therapy and immunotherapy gives new hopes to NSCLC patients, but their outcome/prognosis is far from satisfactory. The translation initiation EIF4F complex has been shown to play important roles in cancer progression. As an important component of the EIF4F complex, EIF4G1 serves as a scaffold and interacts with several other initiation factors such as EIF4E and EIF4A, and help to initiate cap-dependent translation in mammalian cells. EIF4G1 is overexpressed in a variety of cancers, but its functional role, clinical relevance and potential role as a therapeutic target in NSCLC remain largely unknown. Our recent data demonstrate that EIF4G1 expression level is much higher in NSCLC primary tumors than in paired adjacent normal tissues as well as in NSCLC cell lines than in the normal bronchial epithelial cells. Directly targeting EIF4G1 by RNAi or selective small-molecule inhibitors significantly reduce NSCLC cell proliferation, anchorage-independent growth in vitro as well as tumor progression in vivo. Our recent protein array and proteomics analyses indicate that EIF4G1: 1) has a complex interactome network in NSCLC cells; 2) appears to control the expression of a unique subset of the cellular proteome when compared to normal cells, which are closely related to NSCLC cells survival. Taken together, our data support that EIF4G1 plays a critical role in NSCLC survival, oncogenesis and tumor progression, and may serve as a novel and promising therapeutic target for improving NSCLC treatment. Citation Format: Zhiqiang Qin, Lu Dai, Luis Del Valle. Role of EIF4G1 in non-small cell lung cancer pathogenesis and targeted therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4384.