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FGFR
The fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) is a receptor tyrosine kinase (RTK) signaling pathway that fundamentally regulates embryogenesis, angiogenesis, tissue homeostasis, and wound repair. The FGF family contains 22 known ligands and FGFs interact with the extracellular matrix as well as the cell surface via stabilization by heparan sulphate proteoglycans (HSPGs). The communications of FGFs with HSPGs has been shown to be essential for FGF signal transduction. The FGFR receptors (1-4) can become activated by mutation, translocation, or gene amplification. An increase in circulating FGF ligands can also cause activation. Downstream signaling can trigger the mitogen activated protein kinase (MAPK) pathway, the phosphoinositide-3-kinase (PI3K/Akt) pathway, the phosphorylation of the signal transducer and activator of transcription (STAT), and the PLCγ activation of the DAG-PKC and IP3-Ca2+ cascade resulting in DNA transcription. Negative feedback loops can attenuate the signaling cascade at varying levels. The FGFR signaling pathway represents a major target for cancer therapeutics as it plays a crucial role in tumor proliferation, angiogenesis, migration, and survival.
References
1.Chae YK, et al. Oncotarget. 2017;8(9):16052–16074.
References
1.Chae YK, et al. Oncotarget. 2017;8(9):16052–16074.