Implications of Fibroblast Growth Factors (FGFs) in Cancer: From Prognostic to Therapeutic Applications

Author(s): Hassan Dianat-Moghadam, Ladan Teimoori-Toolabi*.

Journal Name: Current Drug Targets

Volume 20 , Issue 8 , 2019

  Journal Home
Translate in Chinese
Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Fibroblast growth factors (FGFs) are pleiotropic molecules exerting autocrine, intracrine and paracrine functions via activating four tyrosine kinase FGF receptors (FGFR), which further trigger a variety of cellular processes including angiogenesis, evasion from apoptosis, bone formation, embryogenesis, wound repair and homeostasis. Four major mechanisms including angiogenesis, inflammation, cell proliferation, and metastasis are active in FGF/FGFR-driven tumors. Furthermore, gain-of-function or loss-of-function in FGFRs1-4 which is due to amplification, fusions, mutations, and changes in tumor–stromal cells interactions, is associated with the development and progression of cancer. Although, the developed small molecule or antibodies targeting FGFR signaling offer immense potential for cancer therapy, emergence of drug resistance, activation of compensatory pathways and systemic toxicity of modulators are bottlenecks in clinical application of anti-FGFRs. In this review, we present FGF/FGFR structure and the mechanisms of its function, as well as cross-talks with other nodes and/or signaling pathways. We describe deregulation of FGF/FGFR-related mechanisms in human disease and tumor progression leading to the presentation of emerging therapeutic approaches, resistance to FGFR targeting, and clinical potentials of individual FGF family in several human cancers. Additionally, the underlying biological mechanisms of FGF/FGFR signaling, besides several attempts to develop predictive biomarkers and combination therapies for different cancers have been explored.

Keywords: Fibroblast growth factor, fibroblast growth factor receptor, cancer, signal transduction, drug resistance, targeted therapy.

[1]
Imamura T. Physiological functions and underlying mechanisms of fibroblast growth factor (FGF) family members: Recent findings and implications for their pharmacological application. Biol Pharm Bull 2014; 37(7): 1081-9.
[2]
Dey D, Nandhini G, Rajkumar K. Fibroblast growth factors and their role in disease and therapy. SRM J Res Dental Sci 2015; 6(1): 41.
[3]
Ohta H, Itoh N. Roles of FGFs as adipokines in adipose tissue development, remodeling, and metabolism. Front Endocrinol 2013; 5: 18.
[4]
Takei Y, Minamizaki T, Yoshiko Y. Functional diversity of fibroblast growth factors in bone formation. Int J Endocrinol 2015; 2015: 729352.
[5]
Raju R, Palapetta SM, Sandhya VK, et al. A network map of FGF- 1/FGFR signaling system. J Signal Transduction 2014; 2014.
[6]
Orr-Urtreger A, Bedford MT, Burakova T, et al. Developmental localization of the splicing alternatives of fibroblast growth factor receptor-2 (FGFR2). Dev Biol 1993; 158(2): 475-86.
[7]
Katoh M, Nakagama H. FGF receptors: cancer biology and therapeutics. Med Res Rev 2014; 34(2): 280-300.
[8]
Presta M, Chiodelli P, Giacomini A, Rusnati M, Ronca R. Fibroblast growth factors (FGFs) in cancer: FGF traps as a new therapeutic approach. Pharmacol Ther 2017; 179: 171-87.
[9]
Goetz R, Beenken A, Ibrahimi OA, et al. Molecular insights into the klotho-dependent, endocrine mode of action of fibroblast growth factor 19 subfamily members. Mol Cell Biol 2007; 27(9): 3417-28.
[10]
Asada M, Shinomiya M, Suzuki M, et al. Glycosaminoglycan affinity of the complete fibroblast growth factor family. Biochimica et Biophysica Acta (BBA)-. General Subjects 2009; 1790(1): 40-8.
[11]
Kurosu H, Kuro-o M. The Klotho gene family as a regulator of endocrine fibroblast growth factors. Mol Cell Endocrinol 2009; 299(1): 72-8.
[12]
Kurosu H, Choi M, Ogawa Y, et al. Tissue-specific expression of βKlotho and fibroblast growth factor (FGF) receptor isoforms determines metabolic activity of FGF19 and FGF21. J Biol Chem 2007; 282(37): 26687-95.
[13]
Bhide RS, Cai Z-W, Zhang Y-Z, et al. Discovery and preclinical studies of (R)-1-(4-(4-Fluoro-2-methyl-1 H-indol-5-yloxy)-5-methylpyrrolo [2, 1-f][1, 2, 4] triazin-6-yloxy) propan-2-ol (BMS-540215), an in vivo active potent VEGFR-2 inhibitor. J Med Chem 2006; 49(7): 2143-6.
[14]
Guo X, Wang X-F. Signaling cross-talk between TGF-β/BMP and other pathways. Cell Res 2009; 19(1): 71-88.
[15]
Pownall ME, Isaacs HV. FGF signalling in vertebrate development Colloquium Series Dev Biol. Colloquium Series Dev Biol 2010: Morgan & Claypool Life Sciences;
[16]
Arend RC, Londoño-Joshi AI, Straughn JM, Buchsbaum DJ. The Wnt/β-catenin pathway in ovarian cancer: A review. Gynecol Oncol 2013; 131(3): 772-9.
[17]
Meng QH, Xu E, Hildebrandt MA, et al. Genetic variants in the fibroblast growth factor pathway as potential markers of ovarian cancer risk, therapeutic response, and clinical outcome. Clin Chem 2014; 60(1): 222-32.
[18]
McGrew LL, Hoppler S, Moon RT. Wnt and FGF pathways cooperatively pattern anteroposterior neural ectoderm in Xenopus. Mech Dev 1997; 69(1): 105-14.
[19]
Kotoh M, Katoh M. Cross-talk of WNT and FGF signaling pathways at GSK3β to regulate β-catenin and SNAIL signaling cascades. Cancer Biol Ther 2006; 5(9): 1059-64.
[20]
Dyer C, Blanc E, Hanisch A, et al. A bi-modal function of Wnt signalling directs an FGF activity gradient to spatially regulate neuronal differentiation in the midbrain. Development 2014; 141(1): 63-72.
[21]
Lovis P, Roggli E, Laybutt DR, et al. Alterations in microRNA expression contribute to fatty acid-induced pancreatic β-cell dysfunction. Diabetes 2008; 57(10): 2728-36.
[22]
Lin W-h, Xiang L-J, Shi H-X, et al. Fibroblast growth factors stimulate hair growth through β-catenin and Shh expression in C57BL/6 mice. BioMed Res Int 2015; 2015.
[23]
Kolligs FT, Bommer G, Göke B. Wnt/beta-catenin/tcf signaling: A critical pathway in gastrointestinal tumorigenesis. Digestion 2002; 66(3): 131-44.
[24]
Shimokawa T, Furukawa Y, Sakai M, et al. Involvement of the FGF18 gene in colorectal carcinogenesis, as a novel downstream target of the β-catenin/T-cell factor complex. Cancer Res 2003; 63(19): 6116-20.
[25]
Teimoori-Toolabi L, Azadmanesh K, Jamali S, et al. Studying the activity of fibroblast growth factor 18 and urokinase plasminogen activator receptor promoters in two colon cancer cell lines. Yakhteh Med J 2009; 11(2): 142-53.
[26]
Teimoori-Toolabi L, Azadmanesh K, Amanzadeh A, Zeinali S. Selective suicide gene therapy of colon cancer exploiting the urokinase plasminogen activator receptor promoter. BioDrugs 2010; 24(2): 131-46.
[27]
Teimoori-Toolabi L, Azadmanesh K, Zeinali S. Selective suicide gene therapy of colon cancer cell lines exploiting fibroblast growth factor 18 promoter. Cancer Biother Radiopharm 2010; 25(1): 105-16.
[28]
Turner N, Grose R. Fibroblast growth factor signalling: From development to cancer. Nat Rev Cancer 2010; 10(2): 116-29.
[29]
Teven CM, Farina EM, Rivas J, Reid RR. Fibroblast growth factor (FGF) signaling in development and skeletal diseases. Genes Dis 2014; 1(2): 199-213.
[30]
Noe EJ, Yoo HW, Kim KN, Lee SY. A case of thanatophoric dysplasia type I with an R248C mutation in the FGFR3 gene. Korean J Pediatr 2010; 53(12): 1022-5.
[31]
Schaefer E, Minoux M, Lauer J, et al. A novel mutation involving the initiation codon of fgf3 in a family described with complete inner ear agenesis, microtia and major microdontia (LAMM Syndrome). J Genetic Syndromes Gene Ther 2014; 2014.
[32]
Yeh E, Fanganiello RD, Sunaga DY, et al. Novel molecular pathways elicited by mutant FGFR2 may account for brain abnormalities in Apert syndrome. PLoS One 2013; 8(4): e60439.
[33]
Percival CJ, Wang Y, Zhou X, Jabs EW, Richtsmeier JT. The effect of a Beare‐Stevenson syndrome Fgfr2 Y394C mutation on early craniofacial bone volume and relative bone mineral density in mice. J Anat 2012; 221(5): 434-42.
[34]
Cornejo-Roldan LR, Roessler E, Muenke M. Analysis of the mutational spectrum of the FGFR2 gene in Pfeiffer syndrome. Hum Genet 1999; 104(5): 425-31.
[35]
McLendon R, Friedman A, Bigner D, et al. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 2008; 455(7216): 1061-8.
[36]
Weiss J, Sos ML, Seidel D, et al. Frequent and focal FGFR1 amplification associates with therapeutically tractable FGFR1 dependency in squamous cell lung cancer Sci Translational Med 2010; 2(62): 62ra93-62ra93.
[37]
Turner N, Pearson A, Sharpe R, et al. FGFR1 amplification drives endocrine therapy resistance and is a therapeutic target in breast cancer. Cancer Res 2010; 70(5): 2085-94.
[38]
Sheu M-J, Hsieh M-J, Chiang W-L, et al. Fibroblast growth factor receptor 4 polymorphism is associated with liver cirrhosis in hepatocarcinoma. PLoS One 2015; 10(4): e0122961.
[39]
Turkington R, Longley D, Allen W, et al. Fibroblast growth factor receptor 4 (FGFR4): A targetable regulator of drug resistance in colorectal cancer. Cell Death Dis 2014; 5(2): e1046.
[40]
Azorsa DO, Gonzales IM, Arora S, et al. RNAi screening identifies FGFR4 as a modulator of growth and survival in Ewing sarcoma. Cancer Res 2014; 74(19)(Suppl.): 3422.
[41]
Williams SV, Hurst CD, Knowles MA. Oncogenic FGFR3 gene fusions in bladder cancer. Hum Mol Genet 2013; 22(4): 795-803.
[42]
Wu Y-M, Su F, Kalyana-Sundaram S, et al. Identification of targetable FGFR gene fusions in diverse cancers. Cancer Discov 2013; 3(6): 636-47.
[43]
Babina IS, Turner NC. Advances and challenges in targeting FGFR signalling in cancer. Nat Rev Cancer 2017; 17(5): 318.
[44]
Nakanishi Y, Akiyama N, Tsukaguchi T, et al. Mechanism of oncogenic signal activation by the novel fusion kinase FGFR3-BAIAP2L1. Mol Cancer Ther 2015; 14(3): 704-12.
[45]
Di Stefano AL, Fucci A, Frattini V, et al. Detection, characterization, and inhibition of FGFR–TACC fusions in IDH wild-type glioma. Clin Cancer Res 2015; 21(14): 3307-17.
[46]
Network CGAR. Comprehensive molecular characterization of urothelial bladder carcinoma. Nature 2014; 507(7492): 315-22.
[47]
Majewski IJ, Mittempergher L, Davidson NM, et al. Identification of recurrent FGFR3 fusion genes in lung cancer through kinome‐centred RNA sequencing. J Pathol 2013; 230(3): 270-6.
[48]
Parker BC, Annala MJ, Cogdell DE, et al. The tumorigenic FGFR3-TACC3 gene fusion escapes miR-99a regulation in glioblastoma. J Clin Investigation 2013;123(2): 0.
[49]
Tan Y, Wang KY, Wang N, Li G, Liu D. Ectopic expression of human acidic fibroblast growth factor 1 in the medicinal plant, Salvia miltiorrhiza, accelerates the healing of burn wounds. BMC Biotechnol 2014; 14(1): 1.
[50]
Capelletti M, Dodge ME, Ercan D, et al. Identification of recurrent fgfr3-tacc3 fusion oncogenes from lung adenocarcinoma. Clin Cancer Res 2014; 20(24): 6551-8.
[51]
Coleman SJ, Bruce C, Chioni A-M, Kocher HM, Grose RP. The ins and outs of fibroblast growth factor receptor signalling. Clin Sci 2014; 127(4): 217-31.
[52]
Levy-Adam F, Ilan N, Vlodavsky I, Eds. Tumorigenic and adhesive properties of heparanase Seminars in cancer biology. 2010: Elsevier.
[53]
Bohrer LR, Schwertfeger KL. Macrophages promote fibroblast growth factor receptor-driven tumor cell migration and invasion in a CXCR2-dependent manner. Mol Cancer Res 2012; 10(10): 1294-305.
[54]
Presta M, Dell’Era P, Mitola S, et al. Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis. Cytokine Growth Factor Rev 2005; 16(2): 159-78.
[55]
Mori S, Tran V, Nishikawa K, et al. A dominant-negative FGF1 mutant (the R50E mutant) suppresses tumorigenesis and angiogenesis. PLoS One 2013; 8(2): e57927.
[56]
Tsunoda S, Nakamura T, Sakurai H, Saiki I. Fibroblast growth factor‐2‐induced host stroma reaction during initial tumor growth promotes progression of mouse melanoma via vascular endothelial growth factor A‐dependent neovascularization. Cancer Sci 2007; 98(4): 541-8.
[57]
Nissen LJ, Cao R, Hedlund E-M, et al. Angiogenic factors FGF2 and PDGF-BB synergistically promote murine tumor neovascularization and metastasis. J Clin Invest 2007; 117(10): 2766-77.
[58]
Cao R, Bråkenhielm E, Pawliuk R, et al. Angiogenic synergism, vascular stability and improvement of hind-limb ischemia by a combination of PDGF-BB and FGF-2. Nat Med 2003; 9(5): 604-13.
[59]
Doukas J, Blease K, Craig D, et al. Delivery of FGF genes to wound repair cells enhances arteriogenesis and myogenesis in skeletal muscle. Mol Ther 2002; 5(5): 517-27.
[60]
Mori S, Wu C-Y, Yamaji S, et al. Direct binding of integrin αvβ3 to FGF1 plays a role in FGF1 signaling. J Biol Chem 2008; 283(26): 18066-75.
[61]
Cao Y. Why and how do tumors stimulate lymphangiogenesis? Lymphat Res Biol 2008; 6(3-4): 145-8.
[62]
Cao R, Lim S, Ji H, et al. Mouse corneal lymphangiogenesis model. Nat Protoc 2011; 6(6): 817-26.
[63]
Cao R, Ji H, Feng N, et al. Collaborative interplay between FGF-2 and VEGF-C promotes lymphangiogenesis and metastasis. Proc Natl Acad Sci 2012; 109(39): 15894-9.
[64]
Jonker JW, Suh JM, Atkins AR, et al. A PPAR [ggr]-FGF1 axis is required for adaptive adipose remodelling and metabolic homeostasis. Nature 2012; 485(7398): 391-4.
[65]
Suh JM, Jonker JW, Ahmadian M, et al. Endocrinization of FGF1 produces a neomorphic and potent insulin sensitizer. Nature 2014; 513(7518): 436-9.
[66]
Onuma Y, Higuchi K, Aiki Y, et al. A Stable chimeric fibroblast growth factor (fgf) can successfully replace basic fgf in human pluripotent stem cell culture. PLoS One 2015; 10(4): e0118931.
[67]
Facchiano A, Russo K, Facchiano AM, et al. Identification of a novel domain of fibroblast growth factor 2 controlling its angiogenic properties. J Biol Chem 2003; 278(10): 8751-60.
[68]
Fan L, Xie H, Chen L, et al. A novel FGF2 antagonist peptide P8 with potent antiproliferation activity. Tumour Biol 2014; 35(10): 10571-9.
[69]
Katoh M. Therapeutics targeting FGF signaling network in human diseases. Trends Pharmacol Sci 2016; 37(12): 1081-96.
[70]
Preusser M, Berghoff AS, Berger W, et al. High rate of FGFR1 amplifications in brain metastases of squamous and non-squamous lung cancer. Lung Cancer 2014; 83(1): 83-9.
[71]
Wendt MK, Taylor MA, Schiemann BJ, Sossey-Alaoui K, Schiemann WP. Fibroblast growth factor receptor splice variants are stable markers of oncogenic transforming growth factor-beta1 signaling in metastatic breast cancers. Breast Cancer Res 2014; 16(2): R24.
[72]
Shi H, Fu C, Wang W, et al. The FGF‐1‐specific single‐chain antibody scFv1C9 effectively inhibits breast cancer tumour growth and metastasis. J Cell Mol Med 2014; 18(10): 2061-70.
[73]
Desnoyers L, Pai R, Ferrando R, et al. Targeting FGF19 inhibits tumor growth in colon cancer xenograft and FGF19 transgenic hepatocellular carcinoma models. Oncogene 2008; 27(1): 85-97.
[74]
Zhao W-m, Wang L, Park H, et al. Monoclonal antibodies to fibroblast growth factor receptor 2 effectively inhibit growth of gastric tumor xenografts. Clin Cancer Res 2010; 16(23): 5750-8.
[75]
Trudel S, Stewart AK, Rom E, et al. The inhibitory anti-FGFR3 antibody, PRO-001, is cytotoxic to t (4; 14) multiple myeloma cells. Blood 2006; 107(10): 4039-46.
[76]
Aono Y, Hasegawa H, Yamazaki Y, et al. Anti‐FGF‐23 neutralizing antibodies ameliorate muscle weakness and decreased spontaneous movement of Hyp mice. J Bone Miner Res 2011; 26(4): 803-10.
[77]
Qing J, Du X, Chen Y, et al. Antibody-based targeting of FGFR3 in bladder carcinoma and t (4; 14)-positive multiple myeloma in mice. J Clin Invest 2009; 119(5): 1216-29.
[78]
Matsuda Y, Shinji S, Yoshimura H, Naito Z, Ishiwata T. Fibroblast growth factor receptor-2 IIIc as a novel molecular target in colorectal cancer. Current Col Cancer Rep 2014; 10(1): 20-6.
[79]
Katoh M. Therapeutics targeting fgf signaling network in human diseases. Trends Pharmacol Sci 2016; 37(12): 1081-96.
[80]
Sun HD, Malabunga M, Tonra JR, et al. Monoclonal antibody antagonists of hypothalamic FGFR1 cause potent but reversible hypophagia and weight loss in rodents and monkeys. Am J Physiol Endocrinol Metab 2007; 292(3): E964-76.
[81]
Agrawal N, Dasaradhi P, Mohmmed A, et al. RNA interference: Biology, mechanism, and applications. Microbiol Mol Biol Rev 2003; 67(4): 657-85.
[82]
Chen D-b, Wang W. Human placental microRNAs and preeclampsia. Biol Reprod 2013; 88(5): 130.
[83]
Katoh M. RNA technology targeted to the WNT signaling pathway. Cancer Biol Ther 2008; 7(2): 275-7.
[84]
Cheng A-L, Shen Y-C, Zhu AX. Targeting fibroblast growth factor receptor signaling in hepatocellular carcinoma. Oncol 2012; 81(5-6): 372-80.
[85]
Shah CA, Bei L, Wang H, Platanias LC, Eklund EA. The leukemia-associated Mll-Ell oncoprotein induces fibroblast growth factor 2 (Fgf2)-dependent cytokine hypersensitivity in myeloid progenitor cells. J Biol Chem 2013; 288(45): 32490-505.
[86]
Zaid TM, Yeung T-L, Thompson MS, et al. Identification of FGFR4 as a potential therapeutic target for advanced-stage, high-grade serous ovarian cancer. Clin Cancer Res 2013; 19(4): 809-20.
[87]
Adas G, Percem A, Adas M, et al. VEGF-A and FGF gene therapy accelerate healing of ischemic colonic anastomoses (experimental study). Int J Surg 2011; 9(6): 467-71.
[88]
Morishita R, Aoki M, Ogihara T. Does gene therapy become pharmacotherapy? Exp Physiol 2005; 90(3): 307-13.
[89]
Maruta F, Parker AL, Fisher KD, et al. Identification of FGF receptor-binding peptides for cancer gene therapy. Cancer Gene Ther 2002; 9(6): 543-52.
[90]
Sonpavde G, Willey CD, Sudarshan S. Fibroblast growth factor receptors as therapeutic targets in clear-cell renal cell carcinoma. Expert Opin Investig Drugs 2014; 23(3): 305-15.
[91]
Porta C, Paglino C, Imarisio I, et al. Changes in circulating pro-angiogenic cytokines, other than VEGF, before progression to sunitinib therapy in advanced renal cell carcinoma patients. Oncol 2012; 84(2): 115-22.
[92]
Fallah A, Sadeghinia A, Kahroba H, et al. Therapeutic targeting of angiogenesis molecular pathways in angiogenesis-dependent diseases. Biomed Pharmacother 2019; 110: 775-85.
[93]
Gavine PR, Mooney L, Kilgour E, et al. AZD4547: An orally bioavailable, potent, and selective inhibitor of the fibroblast growth factor receptor tyrosine kinase family. Cancer Res 2012; 72(8): 2045-56.
[94]
Soria J-C, DeBraud F, Bahleda R, et al. Phase I/IIa study evaluating the safety, efficacy, pharmacokinetics, and pharmacodynamics of lucitanib in advanced solid tumors. Ann Oncol 2014; 25(11): 2244-51.
[95]
Katoh M. Fibroblast growth factor receptors as treatment targets in clinical oncology. Nat Rev Clin Oncol 2019; 16(2): 105-22.
[96]
Sohl CD, Ryan MR, Luo B, Frey KM, Anderson KS. Illuminating the molecular mechanisms of tyrosine kinase inhibitor resistance for the fgfr1 gatekeeper mutation: The achilles’ heel of targeted therapy. ACS Chem Biol 2015; 10(5): 1319-29.
[97]
Zhou Y-X, Pannu R, Le TQ, Armstrong RC. Fibroblast growth factor 1 (FGFR1) modulation regulates repair capacity of oligodendrocyte progenitor cells following chronic demyelination. Neurobiol Dis 2012; 45(1): 196-205.
[98]
Vargas MR, Pehar M, Cassina P, et al. Fibroblast growth factor-1 induces heme oxygenase-1 via nuclear factor erythroid 2-related factor 2 (nrf2) in spinal cord astrocytes consequences for motor neuron survival. J Biol Chem 2005; 280(27): 25571-9.
[99]
Mohan H, Friese A, Albrecht S, et al. Transcript profiling of different types of multiple sclerosis lesions yields FGF1 as a promoter of remyelination. Acta Neuropathol Commun 2014; 2(1): 1.
[100]
Soleyman MR, Khalili M, Khansarinejad B, Baazm M. High-level expression and purification of active human FGF-2 in Escherichia coli by codon and culture condition optimization. Iran Red Crescent Med J 2016; 18(2): e21615.
[101]
Presta M, Leali D, Stabile H, et al. Heparin derivatives as angiogenesis inhibitors. Curr Pharm Des 2003; 9(7): 553-66.
[102]
Murakami M, Simons M. Fibroblast growth factor regulation of neovascularization. Curr Opin Hematol 2008; 15(3): 215.
[103]
Zetter BR. The scientific contributions of M. Judah Folkman to cancer research. Nat Rev Cancer 2008; 8(8): 647-54.
[104]
Kurschat P, Eming S, Nashan D, Krieg T, Mauch C. Early increase in serum levels of the angiogenesis‐inhibitor endostatin and of basic fibroblast growth factor in melanoma patients during disease progression. Br J Dermatol 2007; 156(4): 653-8.
[105]
Xiao L, Yang S, Hao J, et al. Endostar attenuates melanoma tumor growth via its interruption of b-FGF mediated angiogenesis. Cancer Lett 2015; 359(1): 148-54.
[106]
Sonmez AB, Castelnuovo J. Applications of basic fibroblastic growth factor (FGF‐2, bFGF) in dentistry. Dent Traumatol 2014; 30(2): 107-11.
[107]
Hatch N, Franceschi R. FGF2 induced expression of the pyrophosphate generating enzyme, PC-1, is mediated by Runx2 and Msx2. J Musculoskelet Neuronal Interact 2008; 8(4): 318.
[108]
Kitamura C, Nishihara T, Terashita M, Tabata Y, Washio A. Local regeneration of dentin-pulp complex using controlled release of FGF-2 and naturally derived sponge-like scaffolds. Int J Dentistry 2011; 2012.
[109]
Tuna EB, Arai K, Tekkesin MS, et al. Effect of fibroblast growth factor and enamel matrix derivative treatment on root resorption after delayed replantation. Dent Traumatol 2015; 31(1): 49-56.
[110]
Kim J, Park JC, Kim SH, et al. Treatment of FGF‐2 on stem cells from inflamed dental pulp tissue from human deciduous teeth. Oral Dis 2014; 20(2): 191-204.
[111]
Wolf WA, Martin JL, Kartje GL, Farrer RG. Evidence for fibroblast growth factor-2 as a mediator of amphetamine-enhanced motor improvement following stroke. PLoS One 2014; 9(9): e108031.
[112]
Bachis A, Mallei A, Cruz MI, Wellstein A, Mocchetti I. Chronic antidepressant treatments increase basic fibroblast growth factor and fibroblast growth factor-binding protein in neurons. Neuropharmacology 2008; 55(7): 1114-20.
[113]
Catalfamo DL, Britten TM, Storch DI, et al. Hyperglycemia induced and intrinsic alterations in type 2 diabetes‐derived osteoclast function. Oral Dis 2013; 19(3): 303-12.
[114]
Fadini GP, Miorin M, Facco M, et al. Circulating endothelial progenitor cells are reduced in peripheral vascular complications of type 2 diabetes mellitus. J Am Coll Cardiol 2005; 45(9): 1449-57.
[115]
Wallner C, Schira J, Wagner JM, et al. Application of VEGFA and FGF-9 enhances angiogenesis, osteogenesis and bone remodeling in type 2 diabetic long bone regeneration. PLoS One 2015; 10(3): e0118823.
[116]
Asaki T, Konishi M, Miyake A, et al. Roles of fibroblast growth factor 10 (Fgf10) in adipogenesis in vivo. Mol Cell Endocrinol 2004; 218(1): 119-28.
[117]
Konishi M, Asaki T, Koike N, et al. Role of Fgf10 in cell proliferation in white adipose tissue. Mol Cell Endocrinol 2006; 249(1): 71-7.
[118]
Taniguchi F, Harada T, Sakamoto Y, et al. Activation of mitogen-activated protein kinase pathway by keratinocyte growth factor or fibroblast growth factor-10 promotes cell proliferation in human endometrial carcinoma cells. J Clin Endocrinol Metab 2003; 88(2): 773-80.
[119]
Itoh N, Ohta H. Roles of FGFs as adipokines in adipose tissue development, remodeling, and metabolism. Front Endocrinol 2014; 5: 18.
[120]
Li Y-H, Yang L-Y, Chen W, Li Y-K, Yuan H-B. Fibroblast growth factor 10 protects neuron against oxygen-glucose deprivation injury through inducing heme oxygenase-1. Biochem Biophys Res Commun 2015; 456(1): 225-31.
[121]
Patel M, Harrison S, Sinclair R. Drugs and hair loss. Dermatol Clin 2013; 31(1): 67-73.
[122]
Nakayama F, Yasuda T, Umeda S, et al. Fibroblast growth factor-12 (FGF12) translocation into intestinal epithelial cells is dependent on a novel cell-penetrating peptide domain involvement of internalization in the in vivo role of exogenous FGF12. J Biol Chem 2011; 286(29): 25823-34.
[123]
Nakayama F, Umeda S, Yasuda T, et al. Cellular internalization of fibroblast growth factor-12 exerts radioprotective effects on intestinal radiation damage independently of FGFR signaling. Int J Radiat Oncol Biol Phys 2014; 88(2): 377-84.
[124]
Jiang X, Skibba M, Zhang C, et al. The roles of fibroblast growth factors in the testicular development and tumor. J Diabetes Res 2013; 2013.
[125]
Liu W-Y, Xie D-M, Zhu G-Q, et al. Targeting fibroblast growth factor 19 in liver disease: A potential biomarker and therapeutic target. Expert Opin Ther Targets 2015; 19(5): 675-85.
[126]
Walters JR. Bile acid diarrhoea and FGF19: New views on diagnosis, pathogenesis and therapy. Nat Rev Gastroenterol Hepatol 2014; 11(7): 426-34.
[127]
Degirolamo C, Sabbà C, Moschetta A. Therapeutic potential of the endocrine fibroblast growth factors FGF19, FGF21 and FGF23. Nat Rev Drug Discov 2015; 15: 51.
[128]
Schreuder TC, Marsman HA, Lenicek M, et al. The hepatic response to FGF19 is impaired in patients with nonalcoholic fatty liver disease and insulin resistance. Am J Physiol Gastrointest Liver Physiol 2010; 298(3): G440-5.
[129]
Alisi A, Ceccarelli S, Panera N, et al. Association between serum atypical fibroblast growth factors 21 and 19 and pediatric nonalcoholic fatty liver disease. PLoS One 2013; 8(6): e67160.
[130]
Fu T, Choi S-E, Kim D-H, et al. Aberrantly elevated microRNA-34a in obesity attenuates hepatic responses to FGF19 by targeting a membrane coreceptor β-Klotho. Proc Natl Acad Sci 2012; 109(40): 16137-42.
[131]
Gauglhofer C, Paur J, Schrottmaier WC, et al. Fibroblast growth factor receptor 4: A putative key driver for the aggressive phenotype of hepatocellular carcinoma. Carcinogenesis 2014; bgu151.
[132]
Van Der Walt JM, Noureddine MA, Kittappa R, et al. Fibroblast growth factor 20 polymorphisms and haplotypes strongly influence risk of Parkinson disease. Am J Hum Genet 2004; 74(6): 1121-7.
[133]
Shi H-X, Lin C, Lin B-B, et al. The anti-scar effects of basic fibroblast growth factor on the wound repair in vitro and in vivo. PLoS One 2013; 8(4): e59966.
[134]
Liu J-J, Foo JP, Liu S, Lim SC. The role of fibroblast growth factor 21 in diabetes and its complications: A review from clinical perspective. Diabetes Res Clin Pract 2015; 108(3): 382-9.
[135]
Kharitonenkov A, Shiyanova TL, Koester A, et al. FGF-21 as a novel metabolic regulator. J Clin Invest 2005; 115(6): 1627-35.
[136]
Tohyama O, Imura A, Iwano A, et al. Klotho is a novel β-glucuronidase capable of hydrolyzing steroid β-glucuronides. J Biol Chem 2004; 279(11): 9777-84.
[137]
Tsuji K, Maeda T, Kawane T, Matsunuma A, Horiuchi N. Leptin stimulates fibroblast growth factor 23 expression in bone and suppresses renal 1α, 25‐dihydroxyvitamin D3 synthesis in leptin‐deficient ob/ob Mice. J Bone Miner Res 2010; 25(8): 1711-23.
[138]
Shimada T, Hasegawa H, Yamazaki Y, et al. FGF‐23 is a potent regulator of vitamin D metabolism and phosphate homeostasis. J Bone Miner Res 2004; 19(3): 429-35.
[139]
Krajisnik T, Björklund P, Marsell R, et al. Fibroblast growth factor-23 regulates parathyroid hormone and 1α-hydroxylase expression in cultured bovine parathyroid cells. J Endocrinol 2007; 195(1): 125-31.
[140]
Shimada T, Kakitani M, Yamazaki Y, et al. Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism. J Clin Invest 2004; 113(4): 561-8.
[141]
Nitta K, Nagano N, Tsuchiya K. Fibroblast growth factor 23/klotho axis in chronic kidney disease. Nephron Clin Pract 2014; 128(1-2): 1-10.
[142]
Isakova T, Wahl P, Vargas GS, et al. Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease. Kidney Int 2011; 79(12): 1370-8.
[143]
Marsell R, Krajisnik T, Göransson H, et al. Gene expression analysis of kidneys from transgenic mice expressing fibroblast growth factor-23. Nephrol Dial Transplant 2008; 23(3): 827-33.
[144]
Andrukhova O, Smorodchenko A, Egerbacher M, et al. FGF23 promotes renal calcium reabsorption through the TRPV5 channel. The EMBO J 2014; e201284188.
[145]
Andrukhova O, Slavic S, Smorodchenko A, et al. FGF23 regulates renal sodium handling and blood pressure. EMBO Mol Med 2014; e201303716.
[146]
Heine GH, Seiler S, Fliser D. FGF-23: The rise of a novel cardiovascular risk marker in CKD. Nephrol Dial Transplant 2012; 27(8): 3072-81.
[147]
Zhang X, Ibrahimi OA, Olsen SK, et al. Receptor specificity of the fibroblast growth factor family The complete mammalian fgf family. J Biol Chem 2006; 281(23): 15694-700.
[148]
Cheng H, Liao K-K, Liao S-F, Chuang T-Y, Shih Y-H. Spinal cord repair with acidic fibroblast growth factor as a treatment for a patient with chronic paraplegia. Spine 2004; 29(14): E284-8.
[149]
Henry TD, Grines CL, Watkins MW, et al. Effects of Ad5FGF-4 in patients with angina: An analysis of pooled data from the AGENT-3 and AGENT-4 trials. J Am Coll Cardiol 2007; 50(11): 1038-46.
[150]
Hébert JM, Rosenquist T, Götz J, Martin GR. FGF5 as a regulator of the hair growth cycle: Evidence from targeted and spontaneous mutations. Cell 1994; 78(6): 1017-25.
[151]
Steiling H, Werner S. Fibroblast growth factors: Key players in epithelial morphogenesis, repair and cytoprotection. Curr Opin Biotechnol 2003; 14(5): 533-7.
[152]
Moore E, Bendele A, Thompson D, et al. Fibroblast growth factor-18 stimulates chondrogenesis and cartilage repair in a rat model of injury-induced osteoarthritis. Osteoarthritis Cartilage 2005; 13(7): 623-31.
[153]
Takagi Y, Takahashi J, Saiki H, et al. Dopaminergic neurons generated from monkey embryonic stem cells function in a Parkinson primate model. J Clin Invest 2005; 115(1): 102-9.
[154]
Wente W, Efanov AM, Brenner M, et al. Fibroblast growth factor-21 improves pancreatic β-cell function and survival by activation of extracellular signal-regulated kinase 1/2 and Akt signaling pathways. Diabetes 2006; 55(9): 2470-8.
[155]
Aono Y, Shimada T, Yamazaki Y, et al. The neutralization of FGF- 23 ameliorates hypophosphatemia and rickets in Hyp mice. Journal of Bone and Mineral Research; 2003: Amer Soc Bone & Mineral Res 2025 M St, Nw, Ste 800, Washington, DC 20036-3309 USA.
[156]
Tsimafeyeu I, Bratslavsky G. Fibroblast growth factor receptor 1 as a target for the therapy of renal cell carcinoma. Oncol 2015; 88(6): 321-31.
[157]
Inokuchi M, Fujimori Y, Otsuki S, et al. Therapeutic targeting of fibroblast growth factor receptors in gastric cancer. Gastroenterology Res Practice 2015; 2015.
[158]
Ye Y, Shi Y, Zhou Y, et al. The fibroblast growth factor receptor-4 Arg388 allele is associated with gastric cancer progression. Ann Surg Oncol 2010; 17(12): 3354-61.
[159]
Roth GJ, Heckel A, Colbatzky F, et al. Design, synthesis, and evaluation of indolinones as triple angiokinase inhibitors and the discovery of a highly specific 6-methoxycarbonyl-substituted indolinone (BIBF 1120). J Med Chem 2009; 52(14): 4466-80.
[160]
Qiu H, Yashiro M, Zhang X, Miwa A, Hirakawa KA. FGFR2 inhibitor, Ki23057, enhances the chemosensitivity of drug-resistant gastric cancer cells. Cancer Lett 2011; 307(1): 47-52.
[161]
Hutson TE. Targeted therapies for the treatment of metastatic renal cell carcinoma: Clinical evidence. Oncologist 2011; 16(Suppl. 2): 14-22.
[162]
Sherman S, Jarzab B, Cabanillas M, et al. editors. A phase II trial of the multitargeted kinase inhibitor E7080 in advanced radioiodine (RAI)-refractory differentiated thyroid cancer (DTC). ASCO Annual Meeting Proc 2011.
[163]
Lin N, Chen S, Pan W. NP603, a novel and potent inhibitor of FGFR1 tyrosine kinase, inhibits hepatic stellate cell proliferation and ameliorates hepatic fibrosis in rats. Am J Physiol Cell Physiol 2011; 301(2): C469-77.
[164]
Wilhelm SM, Dumas J, Adnane L, et al. Regorafenib (BAY 73‐4506): A new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity. Int J Cancer 2011; 129(1): 245-55.
[165]
Wang G, van der Walt JM, Mayhew G, et al. Variation in the miRNA-433 binding site of FGF20 confers risk for Parkinson disease by overexpression of α-synuclein. Am J Hum Genet 2008; 82(2): 283-9.
[166]
Xu N, Brodin P, Wei T, et al. MiR-125b, a microRNA downregulated in psoriasis, modulates keratinocyte proliferation by targeting FGFR2. J Invest Dermatol 2011; 131(7): 1521-9.
[167]
Tsuchiya S, Fujiwara T, Sato F, et al. MicroRNA-210 regulates cancer cell proliferation through targeting fibroblast growth factor receptor-like 1 (FGFRL1). J Biol Chem 2011; 286(1): 420-8.
[168]
Coleman SJ. Fibroblast growth factor family as a potential target in the treatment of hepatocellular carcinoma. J Hepatocell Carcinoma 2014; 1: 43-54.
[169]
Wu D, Zhou Y, Pan H, Qu P, Zhou J. MicroRNA-99a inhibits cell proliferation, colony formation ability, migration and invasion by targeting fibroblast growth factor receptor 3 in prostate cancer. Mol Med Rep 2015; 11(2): 1469-75.
[170]
Chamorro-Jorganes A, Araldi E, Penalva LO, et al. MicroRNA-16 and microRNA-424 regulate cell-autonomous angiogenic functions in endothelial cells via targeting vascular endothelial growth factor receptor-2 and fibroblast growth factor receptor-1. Arterioscler Thromb Vasc Biol 2011; 31(11): 2595-606.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 20
ISSUE: 8
Year: 2019
Page: [852 - 870]
Pages: 19
DOI: 10.2174/1389450120666190112145409
Price: $58

Article Metrics

PDF: 44
HTML: 2