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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Eleonora Brunello,Matteo Brunelli,Giuseppe Bogina,Anna Caliò,Erminia Manfrin,Alessia Nottegar,Marco Vergine,Annamaria Molino,Emilio Bria,Francesco Massari,Giampaolo Tortora,Sara Cingarlini,Serena Pedron,Marco Chilosi,Giuseppe Zamboni,Keith Miller,Guido Martignoni,Franco Bonetti +17 more
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Different abilities of the four FGFRs to mediate FGF-1 translocation are linked to differences in the receptor C-terminal tail.
Vigdis Sørensen,Antoni G Wiedlocha,Ellen Margrethe Haugsten,Denis Khnykin,Jørgen Wesche,Sjur Olsnes +5 more
TL;DR: A striking diversity in function of the four FGFRs determined by their C-terminal domain is demonstrated, with FGFR1 and FGFR4 able to mediate translocation, whereas FGFR2 andFGFR3 completely lacked this ability.
Journal ArticleDOI
Identification of FGF7 as a novel susceptibility locus for chronic obstructive pulmonary disease.
John Brehm,Koichi Hagiwara,Yohannes Tesfaigzi,Shannon Bruse,Thomas J. Mariani,Soumyaroop Bhattacharya,Nadia Boutaoui,John Ziniti,Manuel E. Soto-Quiros,Lydiana Avila,Michael H. Cho,Blanca E. Himes,Augusto A. Litonjua,Francine L. Jacobson,Per Bakke,Amund Gulsvik,Wayne Anderson,David A. Lomas,Erick Forno,Soma Datta,Edwin K. Silverman,Juan C. Celedón +21 more
TL;DR: Weights constructed from a homozygosity haplotype analysis of an isolated population successfully identify novel genetic associations from a GWAS on a separate population to identify promising candidate genes that fail to meet strict correction for multiple testing.
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Fibroblast growth factor receptor 1 gene amplification in pancreatic ductal adenocarcinoma
Nils C. Lehnen,Anne von Mässenhausen,Holger Kalthoff,Hui Zhou,Tim R. Glowka,Ute Schütte,Tobias Höller,Katarina Riesner,Diana Boehm,Sabine Merkelbach-Bruse,Jutta Kirfel,Sven Perner,Ines Gütgemann +12 more
TL;DR: The gene copy number and expression of fibroblast growth factor receptor 1 (FGFR1) in 155 patients with PDAC are examined, and the effects of the FGFR‐specific inhibitor BGJ398 on FGFR1‐amplified pancreatic tumour cells in vitro are investigated.
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