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Open AccessJournal ArticleDOI

Fibroblast growth factors, their receptors and signaling.

Ciaran Powers, +2 more
- 01 Sep 2000 - 
- Vol. 7, Iss: 3, pp 165-197
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TLDR
FGF signaling also appears to play a role in tumor growth and angiogenesis, and autocrine FGF signaling may be particularly important in the progression of steroid hormone-dependent cancers to a hormone-independent state.
Abstract
Fibroblast growth factors (FGFs) are small polypeptide growth factors, all of whom share in common certain structural characteristics, and most of whom bind heparin avidly. Many FGFs contain signal peptides for secretion and are secreted into the extracellular environment, where theycan bind to the heparan-like glycosaminoglycans (HLGAGs) of the extracellular matrix (ECM). From this reservoir, FGFs mayact directlyon target cells, or theycan be released through digestion of the ECM or the activityof a carrier protein, a secreted FGF binding protein. FGFs bind specific receptor tyrosine kinases in the context of HLGAGs and this binding induces receptor dimerization and activation, ultimatelyresulting in the activation of various signal transduction cascades. Some FGFs are potent angiogenic factors and most playimportant roles in embry onic development and wound healing. FGF signaling also appears to playa role in tumor growth and angiogenesis, and autocrine FGF signaling maybe particularlyimportant in the progression of steroid hormone-dependent cancers to a hormone-independent state.

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Targeting FGF19 inhibits tumor growth in colon cancer xenograft and FGF19 transgenic hepatocellular carcinoma models

TL;DR: It is reported that fibroblast growth factor 19 and its cognate receptor FGF receptor 4 are coexpressed in primary human liver, lung and colon tumors and in a subset of human colon cancer cell lines, and an anti-FGF19 monoclonal antibody is developed that selectively blocks the interaction of FGF19 with FGFR4.
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Irreversible Protein Kinase Inhibitors: Balancing the Benefits and Risks

TL;DR: The therapeutic applicability or the success of irreversible binding kinase inhibitors is dependent on whether or not the covalent bond can be confined solely to the protein kinase of interest.
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Angiogenesis in endocrine tumors.

TL;DR: An understanding of the balance of angiogenesis in these vascular tumors and mechanisms of vascular control may assist in therapeutic decisions and allow appropriately targeted treatment.
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Cross-talk of WNT and FGF signaling pathways at GSK3beta to regulate beta-catenin and SNAIL signaling cascades.

TL;DR: WNT and FGF signaling pathways crosstalk during a variety of cellular processes, such as human colorectal carcinogenesis, mouse mammary tumor virus (MMTV)-induced carcinogenesis and E2A-Pbx-induced leukemogenesis, early embryogenesis, body-axis formation, limb-bud formation, and neurogenesis.
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Fibroblast growth factor signaling controlling osteoblast differentiation.

TL;DR: The elucidation of molecular mechanisms by which FGF signaling promotes osteoblast gene expression and differentiation may help to find novel molecular targets and develop new therapeutic approaches to promote bone formation in human bone disorders.
References
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Journal ArticleDOI

Cell surface, heparin-like molecules are required for binding of basic fibroblast growth factor to its high affinity receptor.

TL;DR: It is demonstrated that free heparin and heparan sulfate can reconstitute a low affinity receptor that is, in turn, required for the high affinity binding of bFGF.
Journal ArticleDOI

Protein modules and signalling networks

TL;DR: This work highlights conserved protein domains that act as key regulatory participants in many of these different signalling pathways in multicellular organisms.
Journal ArticleDOI

Thalidomide is an inhibitor of angiogenesis.

TL;DR: Electron microscopic examination of the corneal neovascularization of thalidomide-treated rabbits revealed specific ultrastructural changes similar to those seen in the deformed limb bud vasculature of Thalidomid-treated embryos.
Journal ArticleDOI

Receptor specificity of the fibroblast growth factor family.

TL;DR: It is demonstrated that FGF 1 is the only FGF that can activate all FGF receptor splice variants and the relative activity of all the other members of the FGF family is determined.
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