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
Fibroblast growth factor receptor 3-IIIc mediates colorectal cancer growth and migration
Gudrun Sonvilla,Sigrid Allerstorfer,Christine Heinzle,Stefan Stättner,Josef Karner,M. Klimpfinger,Fritz Wrba,Hendrik Fischer,Christine Gauglhofer,Sabine Spiegl-Kreinecker,Bettina Grasl-Kraupp,Klaus Holzmann,Michael Grusch,Walter Berger,Brigitte Marian +14 more
TL;DR: The data show that FGFR3-IIIc exerts oncogenic functions by mediating FGF18 effects in colorectal cancer and may constitute a promising new target for therapeutic interventions.
Journal ArticleDOI
Lacrimal Gland Development and Fgf10-Fgfr2b Signaling Are Controlled by 2-O- and 6-O-sulfated Heparan Sulfate
Xiuxia Qu,Christian Carbe,Chenqi Tao,Andrea Powers,Roger Lawrence,Toin H. van Kuppevelt,Wellington V. Cardoso,Kay Grobe,Jeffrey D. Esko,Xin Zhang +9 more
TL;DR: This is the first study to show that simultaneous deletion of Hs2st and Hs6st exhibits profound FGF signaling defects in mammalian development and indicates that Fgf10-Fgfr2b signaling during lacrimal gland development is sensitive to the content or arrangement of O-sulfate groups in heparan sulfate.
Journal ArticleDOI
Fgf9 signaling regulates inner ear morphogenesis through epithelial–mesenchymal interactions
TL;DR: It is shown that, during the precartilage and cartilage stages, Fgf9 is expressed in specific nonsensory domains of the otic epithelium and its receptors, and widely in the surrounding mesenchyme, which gives direct evidence for the existence of reciprocal epithelial-mesenchymal interactions in the developing inner ear.
Journal ArticleDOI
Reciprocal epithelial-mesenchymal FGF signaling is required for cecal development
Xiuqin Zhang,Thaddeus S. Stappenbeck,Andrew C. White,Kory J. Lavine,Jeffrey I. Gordon,David M. Ornitz +5 more
TL;DR: Using epithelial and whole explant cultures, data show that an epithelial FGF9 signal is necessary for the expansion of cecal mesenchyme and the expression of mesenchymal genes that are required for epithelial budding, and these data add to the understanding of FGF-mediated reciprocal epithelial-meschymal signaling.
Journal ArticleDOI
Identification of FGFR4 as a Potential Therapeutic Target for Advanced-Stage, High-Grade Serous Ovarian Cancer
Tarrik M. Zaid,Tsz-Lun Yeung,Melissa S. Thompson,Cecilia S. Leung,Thomas Harding,Ngai Na Co,Rosie S. Schmandt,Suet Ying Kwan,Cristian Rodriguez-Aguay,Gabriel Lopez-Berestein,Anil K. Sood,Kwong Kwok Wong,Michael J. Birrer,Samuel C. Mok +13 more
TL;DR: FGFR4 is a prognostic marker for advanced-stage, high-grade serous ovarian carcinoma and inhibiting ligand-receptor binding significantly decrease ovarian tumor growth both in vitro and in vivo, suggesting that targeting ovarian cancer cells with high levels of FGFR4 protein expression is a new therapeutic modality for this disease and will improve survival of it.
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