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

Hu, P; Chen, H; McGowan, EM; Ren, N; Xu, M; Lin, Y

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

Hu, P Chen, H McGowan, EM

Ren, N Xu, M Lin, Y

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Publication Type:: Journal Article
Citation:: Human Gene Therapy Methods, 2018, 29 (1), pp. 30 - 43
Issue Date:: 2018-02-01

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Field	Value	Language
dc.contributor.author	Hu, P	en_US
dc.contributor.author	Chen, H	en_US
dc.contributor.author	McGowan, EM https://orcid.org/0000-0001-6371-3751	en_US
dc.contributor.author	Ren, N	en_US
dc.contributor.author	Xu, M	en_US
dc.contributor.author	Lin, Y https://orcid.org/0000-0002-4637-9701	en_US
dc.date.available	2017-11-09	en_US
dc.date.issued	2018-02-01	en_US
dc.identifier.citation	Human Gene Therapy Methods, 2018, 29 (1), pp. 30 - 43	en_US
dc.identifier.issn	1946-6536	en_US
dc.identifier.uri	http://hdl.handle.net/10453/120450
dc.description.abstract	© Copyright 2018, Mary Ann Liebert, Inc. 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.	en_US
dc.relation.ispartof	Human Gene Therapy Methods	en_US
dc.relation.isbasedon	10.1089/hgtb.2017.104	en_US
dc.subject.classification	Biotechnology	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Mice, Inbred BALB C	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Lung Neoplasms	en_US
dc.subject.mesh	Neoplasm Proteins	en_US
dc.subject.mesh	Xenograft Model Antitumor Assays	en_US
dc.subject.mesh	Gene Expression Regulation, Enzymologic	en_US
dc.subject.mesh	Gene Expression Regulation, Neoplastic	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Receptor, Fibroblast Growth Factor, Type 1	en_US
dc.subject.mesh	A549 Cells	en_US
dc.subject.mesh	Adenocarcinoma of Lung	en_US
dc.title	Assessment of FGFR1 Over-Expression and Over-Activity in Lung Cancer Cells: A Toolkit for Anti-FGFR1 Drug Screening	en_US
dc.type	Journal Article
utslib.citation.volume	1	en_US
utslib.citation.volume	29	en_US
utslib.for	1004 Medical Biotechnology	en_US
utslib.for	1103 Clinical Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	closed_access
pubs.issue	1	en_US
pubs.publication-status	Published	en_US
pubs.volume	29	en_US

Abstract:

© Copyright 2018, Mary Ann Liebert, Inc. 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.

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http://hdl.handle.net/10453/120450