The Fibroblast Growth Factor signaling pathway
David M. Ornitz,Nobuyuki Itoh +1 more
TLDR
Members of the FGF family function in the earliest stages of embryonic development and during organogenesis to maintain progenitor cells and mediate their growth, differentiation, survival, and patterning.Abstract:
The signaling component of the mammalian Fibroblast Growth Factor (FGF) family is comprised of eighteen secreted proteins that interact with four signaling tyrosine kinase FGF receptors (FGFRs) Interaction of FGF ligands with their signaling receptors is regulated by protein or proteoglycan cofactors and by extracellular binding proteins Activated FGFRs phosphorylate specific tyrosine residues that mediate interaction with cytosolic adaptor proteins and the RAS-MAPK, PI3K-AKT, PLCγ, and STAT intracellular signaling pathways Four structurally related intracellular non-signaling FGFs interact with and regulate the family of voltage gated sodium channels Members of the FGF family function in the earliest stages of embryonic development and during organogenesis to maintain progenitor cells and mediate their growth, differentiation, survival, and patterning FGFs also have roles in adult tissues where they mediate metabolic functions, tissue repair, and regeneration, often by reactivating developmental signaling pathways Consistent with the presence of FGFs in almost all tissues and organs, aberrant activity of the pathway is associated with developmental defects that disrupt organogenesis, impair the response to injury, and result in metabolic disorders, and cancer © 2015 Wiley Periodicals, Incread more
Citations
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Tumor angiogenesis: causes, consequences, challenges and opportunities.
TL;DR: The current understanding of cellular and molecular mechanisms involved in tumor angiogenesis is summarized and challenges and opportunities associated with vascular targeting are discussed.
Journal ArticleDOI
Pegbelfermin (BMS-986036), a PEGylated fibroblast growth factor 21 analogue, in patients with non-alcoholic steatohepatitis: a randomised, double-blind, placebo-controlled, phase 2a trial.
Arun J. Sanyal,Edgar D. Charles,Brent A. Neuschwander-Tetri,Rohit Loomba,Stephen A. Harrison,Manal F. Abdelmalek,Eric Lawitz,Dina Halegoua-DeMarzio,Sudeep Kundu,Stephanie Noviello,Yi Luo,Rose C. Christian +11 more
TL;DR: Treatment with subcutaneously administered pegbelfermin for 16 weeks was generally well tolerated and significantly reduced hepatic fat fraction in patients with non-alcoholic steatohepatitis, and the full planned sample size was not needed.
Journal ArticleDOI
Fibroblast growth factor signaling in skeletal development and disease
TL;DR: Progress made on understanding the functions of the FGF signaling pathway during critical stages of skeletogenesis is examined, and the mechanisms by which mutations in FGF signalling molecules cause skeletal malformations in humans are explored.
Journal ArticleDOI
The molecular basis of endothelial cell plasticity
TL;DR: The endothelium is capable of remarkable plasticity in the embryo and in the adult, maintenance of differentiated endothelial state is an active process requiring constant signalling input that leads to the development of endothelial-to-mesenchymal transition that plays an important role in pathogenesis of a number of diseases.
Journal ArticleDOI
Classifying the evolutionary and ecological features of neoplasms
Carlo C. Maley,Athena Aktipis,Trevor A. Graham,Andrea Sottoriva,Amy M. Boddy,Michalina Janiszewska,Ariosto S. Silva,Marco Gerlinger,Yinyin Yuan,Kenneth J. Pienta,Karen S. Anderson,Robert A. Gatenby,Charles Swanton,David Posada,Chung I. Wu,Joshua D. Schiffman,E. Shelley Hwang,Kornelia Polyak,Alexander R. A. Anderson,Joel S. Brown,Mel Greaves,Darryl Shibata +21 more
TL;DR: A framework for classifying tumours is proposed that holds promise for enabling clinicians to personalize optimal interventions based on the evolvability of the patient's tumour, and the Evo- and Eco-indices provide a common lexicon for communicating about how neoplasms change in response to interventions.
References
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Journal ArticleDOI
Conditional inactivation of Fgfr1 in mouse defines its role in limb bud establishment, outgrowth and digit patterning
TL;DR: The study of these two Fgfr1 conditional mutants has elucidated the multiple roles ofFGFR1 in limb bud establishment, growth and patterning and shown that during autopod patterning, FGFR1 influences digit number and identity, probably through cell-autonomous regulation of Shh expression.
Journal ArticleDOI
A naturally occurring secreted form of fibroblast growth factor (FGF) receptor 1 binds basic FGF in preference over acidic FGF.
TL;DR: The results suggest that this secreted form of FGF receptor has an unusual ligand binding specificity that may be important for its biological role in vivo.
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Cell-Autonomous and Non–Cell-Autonomous Mechanisms of Transformation by Amplified FGFR1 in Lung Cancer
Florian Malchers,Felix Dietlein,Jakob Schöttle,Xin Lu,Lucia Nogova,Kerstin Albus,Lynnette Fernandez-Cuesta,Johannes M. Heuckmann,Oliver Gautschi,Joachim Diebold,Dennis Plenker,Masyar Gardizi,Matthias Scheffler,Marc Bos,Danila Seidel,Frauke Leenders,André Richters,Martin Peifer,Alexandra Florin,Prathama S. Mainkar,Nagaraju Karre,Srivari Chandrasekhar,Julie George,Steffi Silling,Daniel Rauh,Thomas Zander,Roland T. Ullrich,H. Christian Reinhardt,Francois Ringeisen,Reinhard Büttner,Lukas C. Heukamp,Jürgen Wolf,Roman K. Thomas +32 more
TL;DR: It is shown that multiple factors affect the tumorigenic potential of FGFR1, thus providing clinical hypotheses for refinement of patient selection and suggesting implications for patient selection for treatment with FGFR inhibitors.
Journal ArticleDOI
FGF12 is a candidate Brugada syndrome locus
Jessica A. Hennessey,Cherisse A. Marcou,Chuan Wang,Eric Q. Wei,Chaojian Wang,David J. Tester,Margherita Torchio,Federica Dagradi,Lia Crotti,Peter J. Schwartz,Michael J. Ackerman,Geoffrey S. Pitt +11 more
TL;DR: These multilevel investigations strongly suggest that Q7R-FGF12 is a disease-associated BrS mutation, and suggest for the first time that FHF effects on Na(+) and Ca(2+) channels are separable.
Journal ArticleDOI
Identification of extracellular matrix ligands for the heparan sulfate proteoglycan agrin.
TL;DR: Evidence is provided that agrin plays a crucial role in the function of the extracellular matrix and a role for agrin in axon pathway development is suggested and a partial codistribution of agrin and its ECM ligands in the chick developing visual system is revealed.
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