A time-resolved live cell imaging assay to identify small molecule inhibitors of FGF2 signaling.
Cell Line, Tumor
Cell Proliferation
/ drug effects
Cell Survival
/ drug effects
Dose-Response Relationship, Drug
Drug Resistance, Neoplasm
/ drug effects
Drug Screening Assays, Antitumor
Extracellular Signal-Regulated MAP Kinases
/ metabolism
Fibroblast Growth Factor 2
/ metabolism
Gene Expression Regulation, Neoplastic
/ drug effects
Humans
Neuroblastoma
/ drug therapy
Phosphorylation
Receptors, Fibroblast Growth Factor
/ antagonists & inhibitors
Signal Transduction
/ drug effects
Small Molecule Libraries
/ pharmacology
FGF2 signaling
fibroblast growth factor 2
live cell imaging
small molecule inhibitors
tumor cell survival
tumor-induced angiogenesis
Journal
FEBS letters
ISSN: 1873-3468
Titre abrégé: FEBS Lett
Pays: England
ID NLM: 0155157
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
04
04
2019
revised:
18
05
2019
accepted:
24
05
2019
pubmed:
29
5
2019
medline:
6
6
2020
entrez:
29
5
2019
Statut:
ppublish
Résumé
Fibroblast growth factor 2 (FGF2) is a cell survival factor with crucial functions in tumor-induced angiogenesis. Here, we describe a novel time-resolved FGF2 signaling assay based upon live cell imaging of neuroblastoma cells. To validate this system, we tested 8960 small molecules for inhibition of FGF2 signaling with kinetic resolution. Hit compounds were validated in dose-response experiments for FGF2 signaling, FGF receptor antagonism, downstream ERK phosphorylation and FGF2-dependent chemoresistance in a cellular leukemia model system. The new screening system for FGF2 signaling inhibitors has unique features, deselecting compounds with pleiotropic effects on cell proliferation and, along with the experimental pipeline reported, great potential for the discovery of new classes of FGF2 signaling inhibitors that block FGF2 dependent tumor cell survival.
Identifiants
pubmed: 31135968
doi: 10.1002/1873-3468.13462
doi:
Substances chimiques
Receptors, Fibroblast Growth Factor
0
Small Molecule Libraries
0
Fibroblast Growth Factor 2
103107-01-3
Extracellular Signal-Regulated MAP Kinases
EC 2.7.11.24
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2162-2176Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : Ni 423/9-1
Pays : International
Informations de copyright
© 2019 Federation of European Biochemical Societies.
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