机构：[1]Department of Oncology, The First Affiliated Hospital of Jinan University, Guangzhou, China[2]Department of Traditional Chinese Medicine, The Third Affiliated Hospital of Sun Yat- Sen University, Guangzhou, China中山大学附属第三医院[3]School of Life Sciences, University of Technology Sydney, Sydney, Australia[4]Guangdong Online Hospital Clinic, Guangdong 2nd Provincial People’s Hospital, Guangzhou, China
Lung cancer, caused mainly 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 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. A stable lentiviral FGFR1 over-expression system in lung cancer cells is described 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 the laboratory, the overactive PI3K pathway was effectively blocked, 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.
基金：
The study was supported by two research grants from the National Natural Science
Foundation of China (81273814and 81774376) and a special grant from Guangdong
Provincial Key Scientific Research Grant (2013A02210031)
语种：
外文
被引次数：
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2017]版：
大类|4 区医学
小类|4 区生物工程与应用微生物4 区遗传学4 区医学：研究与实验
最新[2025]版：
无
JCR分区：
出版当年[2016]版：
Q3MEDICINE, RESEARCH & EXPERIMENTALQ3BIOTECHNOLOGY & APPLIED MICROBIOLOGYQ3GENETICS & HEREDITY
第一作者机构：[1]Department of Oncology, The First Affiliated Hospital of Jinan University, Guangzhou, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Oncology, The First Affiliated Hospital of Jinan University, Guangzhou, China[3]School of Life Sciences, University of Technology Sydney, Sydney, Australia[*1]School of Life Sciences, University of Technology Sydney, Sydney, Australia.[*2]Department of Oncology, The First Affiliated Hospital of Jinan University, Guangzhou, China.
推荐引用方式(GB/T 7714)：
Penghui Hu,Hongjie Chen,Eileen M McGowan,et al.Assessment of FGFR1 Over-Expression and Over-Activity in Lung Cancer Cells: A Toolkit for Anti-FGFR1 Drug Screening.[J].HUMAN GENE THERAPY METHODS.2018,29(1):30-43.doi:10.1089/hgtb.2017.104.
APA：
Penghui Hu,Hongjie Chen,Eileen M McGowan,Nina Ren,Meng Xu&Yiguang Lin.(2018).Assessment of FGFR1 Over-Expression and Over-Activity in Lung Cancer Cells: A Toolkit for Anti-FGFR1 Drug Screening..HUMAN GENE THERAPY METHODS,29,(1)
MLA：
Penghui Hu,et al."Assessment of FGFR1 Over-Expression and Over-Activity in Lung Cancer Cells: A Toolkit for Anti-FGFR1 Drug Screening.".HUMAN GENE THERAPY METHODS 29..1(2018):30-43
