Assessment of FGFR1 Overexpression and Over-Activity in Lung Cancer Cells: A Toolkit for Anti-FGFR1 Drug Screening

Publisher:
Mary Ann Liebert
Publication Type:
Journal Article
Citation:
Human Gene Therapy, 2017
Issue Date:
2017-11-16
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Lung cancer, mainly caused by smoking, is one of the most prevalent diseases in China resulting in high mortality rates. The increasing incidence of chronic disease due to lung cancer places a huge burden on the welfare and cost to the Chinese society. Amplification of the fibroblast growth factor receptor 1 (FGFR1) is associated with high incidence and mortality in lung cancer patients. FGFR1 signaling is implicated in oncogenic traits such as proliferation, cell survival, angiogenesis and migration. Targeting the FGFR1 and its ligand basic FGF (bFGF) is a key step forward in developing new therapies for this crippling disease. Lung adenocarcinoma is the most common subtype of non-small cell lung cancer. In this study A549, a lung adenocarcinoma cell line widely used in vitro as a model for drug metabolism and as a transfection host, was used to study FGFR1. Here we describe a stable lentiviral FGFR1 overexpression system in lung cancer cells for the study of anti-lung cancer drug candidates targeting FGFR1. Ligand binding to FGFR1 activates the PI3K/Akt/mTOR signaling pathway and increases adhesion, invasion and migration in this model. Using a unique FGF monoclonal antibody developed in our laboratory we effectively blocked the overactive PI3K pathway abrogating the negative metastatic signaling pathways in lung cancer cells. Importantly, this model provides an effective and simple screening kit for anti-FGF1 drug compounds for lung cancer treatment and a tool for understanding the molecular mechanisms of the FGFR1 signaling pathway in lung cancer. Furthermore, this toolkit based on a FGFR1 lentiviral construct model is transferrable to study FGFR1 signaling in any type of cancer cell.
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