fibroblast growth factor 8


Summary: A fibroblast growth factor that preferentially activates FIBROBLAST GROWTH FACTOR RECEPTOR 4. It was initially identified as an androgen-induced growth factor and plays a role in regulating growth of human BREAST NEOPLASMS and PROSTATIC NEOPLASMS.

Top Publications

  1. Shimogori T, Grove E. Fibroblast growth factor 8 regulates neocortical guidance of area-specific thalamic innervation. J Neurosci. 2005;25:6550-60 pubmed
    ..The cortical patterning molecule fibroblast growth factor 8 (FGF8) was misexpressed in the cortical primordium to rearrange the area map...
  2. Armstrong K, Robson C, Leung H. NF-kappaB activation upregulates fibroblast growth factor 8 expression in prostate cancer cells. Prostate. 2006;66:1223-34 pubmed
    b>Fibroblast growth factor 8 (FGF8) is over-expressed in prostate cancer (CaP) correlating with high-grade disease and reduced survival...
  3. Maegawa S, Varga M, Weinberg E. FGF signaling is required for {beta}-catenin-mediated induction of the zebrafish organizer. Development. 2006;133:3265-76 pubmed
  4. Mariani F, Ahn C, Martin G. Genetic evidence that FGFs have an instructive role in limb proximal-distal patterning. Nature. 2008;453:401-5 pubmed publisher
    ..We discuss how a two-signal model for P-D patterning can be integrated with the concept of early specification to explain the genetic data presented here. ..
  5. Li J, Lao Z, Joyner A. New regulatory interactions and cellular responses in the isthmic organizer region revealed by altering Gbx2 expression. Development. 2005;132:1971-81 pubmed
    ..Our studies provide new insights into the regulatory interactions that maintain isthmic organizer gene expression and the consequences of altered levels of organizer gene expression on cell survival. ..
  6. Martinez Ferre A, Martinez S. The development of the thalamic motor learning area is regulated by Fgf8 expression. J Neurosci. 2009;29:13389-400 pubmed publisher
    ..This region specializes to permit the development of adaptive control of the motor function in the vertebrate brain. ..
  7. Mott N, Chung W, Tsai P, Pak T. Differential fibroblast growth factor 8 (FGF8)-mediated autoregulation of its cognate receptors, Fgfr1 and Fgfr3, in neuronal cell lines. PLoS ONE. 2010;5:e10143 pubmed publisher
    ..Together, our data bring forth the possibility that, in addition to the FGF synexpression group, autoregulation of FGFR expression by FGF8 represents a mechanism by which FGF8 could fine-tune its regulatory actions. ..
  8. Wittmann D, Blöchl F, Trumbach D, Wurst W, Prakash N, Theis F. Spatial analysis of expression patterns predicts genetic interactions at the mid-hindbrain boundary. PLoS Comput Biol. 2009;5:e1000569 pubmed publisher
    ..We show, in particular, that the spatial gene expression patterns around the MHB help us to understand the maintenance of this boundary on a systems level. ..
  9. Hernández Martínez R, Castro Obregon S, Covarrubias L. Progressive interdigital cell death: regulation by the antagonistic interaction between fibroblast growth factor 8 and retinoic acid. Development. 2009;136:3669-78 pubmed publisher
    ..Thus, ICD is determined by the antagonistic regulation of cell death by Fgf8 and RA and occurs through a progressive, rather than massive, cell death mechanism. ..

More Information


  1. Hong C, Park B, Saint Jeannet J. Fgf8a induces neural crest indirectly through the activation of Wnt8 in the paraxial mesoderm. Development. 2008;135:3903-10 pubmed publisher
    ..We propose that Fgf8a induces NC indirectly through the activation of Wnt8 in the paraxial mesoderm, which in turn promotes NC formation in the overlying ectoderm primed by Bmp antagonists. ..
  2. Kawata H, Kamiakito T, Takayashiki N, Tanaka A. Vitamin D3 suppresses the androgen-stimulated growth of mouse mammary carcinoma SC-3 cells by transcriptional repression of fibroblast growth factor 8. J Cell Physiol. 2006;207:793-9 pubmed
    ..Moreover, VDR repressed the core promoter activity of fgf8 in COS1 cells and in the SC-3 cells. All these findings strongly suggest that vitamin D3 serves as a negative regulator for both androgen-related and fgf8 transcriptions. ..
  3. Fletcher R, Baker J, Harland R. FGF8 spliceforms mediate early mesoderm and posterior neural tissue formation in Xenopus. Development. 2006;133:1703-14 pubmed publisher
    ..Furthermore, FGF8 signaling is necessary for proper posterior neural formation; loss of either FGF8a or a reduction in both FGF8a and FGF8b causes a reduction in the hindbrain and spinal cord domains...
  4. Alexandre P, Bachy I, Marcou M, Wassef M. Positive and negative regulations by FGF8 contribute to midbrain roof plate developmental plasticity. Development. 2006;133:2905-13 pubmed
    ..Normally, the antagonistic regulatory interactions spread smoothly across the midbrain. Plasticity of midbrain RP differentiation probably results from an experimentally induced imbalance between regulatory pathways. ..
  5. Nilsson E, Brokken L, Härkönen P. Fibroblast growth factor 8 increases breast cancer cell growth by promoting cell cycle progression and by protecting against cell death. Exp Cell Res. 2010;316:800-12 pubmed publisher
    b>Fibroblast growth factor 8 (FGF-8) is expressed in a large proportion of breast cancers, whereas its level in normal mammary gland epithelium is low...
  6. Karbowski J, Ermentrout G. Model of the early development of thalamo-cortical connections and area patterning via signaling molecules. J Comput Neurosci. 2004;17:347-63 pubmed
    ..The model can make predictions and provides a basic mathematical framework for the early development of the thalamo-cortical connections and area patterning that can be further refined as more experimental facts become known. ..
  7. Stottmann R, Tran P, Turbe Doan A, Beier D. Ttc21b is required to restrict sonic hedgehog activity in the developing mouse forebrain. Dev Biol. 2009;335:166-78 pubmed publisher
    ..Finally, we evaluate Wnt signaling but do not find evidence that this plays a role in causing the perturbed neurodevelopmental phenotype we describe. ..
  8. Jaskoll T, Leo T, Witcher D, Ormestad M, Astorga J, Bringas P, et al. Sonic hedgehog signaling plays an essential role during embryonic salivary gland epithelial branching morphogenesis. Dev Dyn. 2004;229:722-32 pubmed
  9. Sahara S, Kawakami Y, Izpisua Belmonte J, O Leary D. Sp8 exhibits reciprocal induction with Fgf8 but has an opposing effect on anterior-posterior cortical area patterning. Neural Dev. 2007;2:10 pubmed
    ..In summary, Sp8 and Fgf8 robustly induce one another, and may act to balance the anterior-posterior area patterning of the cortex. ..
  10. Jaskoll T, Witcher D, Toreno L, Bringas P, Moon A, Melnick M. FGF8 dose-dependent regulation of embryonic submandibular salivary gland morphogenesis. Dev Biol. 2004;268:457-69 pubmed
    ..This is as expected, though there is no synergistic effect with FGF10 + Shh peptide supplementation. These in vitro experiments model the principle that mutations have different effects in the context of different epigenotypes. ..
  11. Zhao X, Sirbu I, Mic F, Molotkova N, Molotkov A, Kumar S, et al. Retinoic acid promotes limb induction through effects on body axis extension but is unnecessary for limb patterning. Curr Biol. 2009;19:1050-7 pubmed publisher
  12. Zelarayan L, Vendrell V, Alvarez Y, Dominguez Frutos E, Theil T, Alonso M, et al. Differential requirements for FGF3, FGF8 and FGF10 during inner ear development. Dev Biol. 2007;308:379-91 pubmed
    ..Together these results provide important insights into how the spatial and temporal expression of various FGFs controls different steps of inner ear formation during vertebrate development. ..
  13. García Hernández S, Potashner S, Morest D. Role of fibroblast growth factor 8 in neurite outgrowth from spiral ganglion neurons in vitro. Brain Res. 2013;1529:39-45 pubmed publisher
    ..factors and neurotrophins delay degeneration and promote regrowth of neural processes, the role of fibroblast growth factor 8 (FGF8) in mammalian spiral ganglion neurons (SGN) neurite outgrowth has not been examined...
  14. Shimada N, Ishii T, Imada T, Takaba K, Sasaki Y, Maruyama Takahashi K, et al. A neutralizing anti-fibroblast growth factor 8 monoclonal antibody shows potent antitumor activity against androgen-dependent mouse mammary tumors in vivo. Clin Cancer Res. 2005;11:3897-904 pubmed
    ..KM1334 possesses strong blocking activity in vitro and antitumor activity in vivo and therefore may be an effective therapeutic candidate for the treatment of cancers that are dependent on FGF8b signaling for growth and survival. ..
  15. Urban A, Zhou X, Ungos J, Raible D, Altmann C, Vize P. FGF is essential for both condensation and mesenchymal-epithelial transition stages of pronephric kidney tubule development. Dev Biol. 2006;297:103-17 pubmed
  16. Kataoka A, Shimogori T. Fgf8 controls regional identity in the developing thalamus. Development. 2008;135:2873-81 pubmed publisher
    ..These findings suggest conserved roles of FGF signaling in patterning along the A/P axis in CNS, and reveal mechanisms of nucleogenesis in the developing thalamus. ..
  17. Cholfin J, Rubenstein J. Frontal cortex subdivision patterning is coordinately regulated by Fgf8, Fgf17, and Emx2. J Comp Neurol. 2008;509:144-55 pubmed publisher
    ..We have integrated our results to propose a model for how fibroblast growth factors regulate FC patterning through regulation of regional transcription factor expression within the FC anlage. ..
  18. Mattila M, Härkönen P. Role of fibroblast growth factor 8 in growth and progression of hormonal cancer. Cytokine Growth Factor Rev. 2007;18:257-66 pubmed
    ..factors which have been associated with the regulation of growth and progression of hormonal cancer is fibroblast growth factor 8 (FGF8) which has also been recognized as an oncogene...
  19. Sterneckert J, Stehling M, Bernemann C, Arauzo Bravo M, Greber B, Gentile L, et al. Neural induction intermediates exhibit distinct roles of Fgf signaling. Stem Cells. 2010;28:1772-81 pubmed publisher
    ..Fgf2 and Fgf8 thus stimulate self-renewal in different cell types. ..
  20. Tarkkonen K, Ruohola J, Härkönen P. Fibroblast growth factor 8 induced downregulation of thrombospondin 1 is mediated by the MEK/ERK and PI3K pathways in breast cancer cells. Growth Factors. 2010;28:256-67 pubmed publisher
    Expression of fibroblast growth factor 8 (FGF-8) is increased in several forms of hormonal cancer. It was previously shown to regulate expression of thrombospondin 1 (TSP-1), an inhibitor of angiogenesis, in S115 breast cancer cells...
  21. Shimogori T, Banuchi V, Ng H, Strauss J, Grove E. Embryonic signaling centers expressing BMP, WNT and FGF proteins interact to pattern the cerebral cortex. Development. 2004;131:5639-47 pubmed
    ..Our findings point to a cross-regulation of BMP, FGF, and WNT signaling in the early telencephalon, integrated by EMX2, and required for normal cortical development. ..
  22. Scholpp S, Groth C, Lohs C, Lardelli M, Brand M. Zebrafish fgfr1 is a member of the fgf8 synexpression group and is required for fgf8 signalling at the midbrain-hindbrain boundary. Dev Genes Evol. 2004;214:285-95 pubmed
    ..The expression patterns of fgfr1 and fgf8 are strikingly similar and knock-down of fgfr1 phenocopies many aspects observed in the fgf8 mutant acerebellar, suggesting that Fgf8 exerts its function mainly by binding to FgfR1. ..
  23. Moldrich R, Gobius I, Pollak T, Zhang J, Ren T, Brown L, et al. Molecular regulation of the developing commissural plate. J Comp Neurol. 2010;518:3645-61 pubmed publisher
    ..The results demonstrate that correct patterning of the commissural plate is an important mechanism in forebrain commissure formation. ..
  24. Lin C, Yin Y, Long F, Ma L. Tissue-specific requirements of beta-catenin in external genitalia development. Development. 2008;135:2815-25 pubmed publisher
  25. Kobayashi T, Yasuda K, Araki M. Coordinated regulation of dorsal bone morphogenetic protein 4 and ventral Sonic hedgehog signaling specifies the dorso-ventral polarity in the optic vesicle and governs ocular morphogenesis through fibroblast growth factor 8 upregulation. Dev Growth Differ. 2010;52:351-63 pubmed publisher
    ..protein 4 (BMP4) and Sonic hedgehog (Shh) constitute a dorsal-ventral signaling system together with fibroblast growth factor 8 (FGF8)...
  26. Suzuki Hirano A, Harada H, Sato T, Nakamura H. Activation of Ras-ERK pathway by Fgf8 and its downregulation by Sprouty2 for the isthmus organizing activity. Dev Biol. 2010;337:284-93 pubmed publisher
  27. Sato T, Joyner A. The duration of Fgf8 isthmic organizer expression is key to patterning different tectal-isthmo-cerebellum structures. Development. 2009;136:3617-26 pubmed publisher
    The isthmic organizer and its key effector molecule, fibroblast growth factor 8 (Fgf8), have been cornerstones in studies of how organizing centers differentially pattern tissues...
  28. Creuzet S. Neural crest contribution to forebrain development. Semin Cell Dev Biol. 2009;20:751-9 pubmed publisher
  29. Storm E, Garel S, Borello U, Hebert J, Martinez S, McConnell S, et al. Dose-dependent functions of Fgf8 in regulating telencephalic patterning centers. Development. 2006;133:1831-44 pubmed
    ..These data suggest that Fgf8 functions to coordinate multiple patterning centers, and that modifications in the relative strength of FGF signaling can have profound effects on the relative size and nature of telencephalic subdivisions. ..
  30. Grieshammer U, Cebrian C, Ilagan R, Meyers E, Herzlinger D, Martin G. FGF8 is required for cell survival at distinct stages of nephrogenesis and for regulation of gene expression in nascent nephrons. Development. 2005;132:3847-57 pubmed
    ..Thus, unlike other FGF family members, which regulate growth and branching morphogenesis of the collecting duct system, Fgf8 encodes a factor essential for gene regulation and cell survival at distinct steps in nephrogenesis. ..
  31. Sirbu I, Duester G. Retinoic-acid signalling in node ectoderm and posterior neural plate directs left-right patterning of somitic mesoderm. Nat Cell Biol. 2006;8:271-7 pubmed
  32. Creuzet S, Martinez S, Le Douarin N. The cephalic neural crest exerts a critical effect on forebrain and midbrain development. Proc Natl Acad Sci U S A. 2006;103:14033-8 pubmed
    ..All together, these findings support the notion that the cephalic NC controls the formation of craniofacial structures and the development of preotic brain. ..
  33. Hester S, Belmonte J, Gens J, Clendenon S, Glazier J. A multi-cell, multi-scale model of vertebrate segmentation and somite formation. PLoS Comput Biol. 2011;7:e1002155 pubmed publisher
  34. Valta M, Tuomela J, Vuorikoski H, Loponen N, Väänänen R, Pettersson K, et al. FGF-8b induces growth and rich vascularization in an orthotopic PC-3 model of prostate cancer. J Cell Biochem. 2009;107:769-84 pubmed publisher
    b>Fibroblast growth factor 8 (FGF-8) is expressed at an increased level in a high proportion of prostate cancers and it is associated with a poor prognosis of the disease...
  35. Okada T, Okumura Y, Motoyama J, Ogawa M. FGF8 signaling patterns the telencephalic midline by regulating putative key factors of midline development. Dev Biol. 2008;320:92-101 pubmed publisher
  36. Gauglhofer C, Sagmeister S, Schrottmaier W, Fischer C, Rodgarkia Dara C, Mohr T, et al. Up-regulation of the fibroblast growth factor 8 subfamily in human hepatocellular carcinoma for cell survival and neoangiogenesis. Hepatology. 2011;53:854-64 pubmed publisher
    ..Thus, the FGF8 subfamily supports the development and progression of hepatocellular malignancy. ..
  37. Sasaki T, Nishihara H, Hirakawa M, Fujimura K, Tanaka M, Kokubo N, et al. Possible involvement of SINEs in mammalian-specific brain formation. Proc Natl Acad Sci U S A. 2008;105:4220-5 pubmed publisher
    ..Using a mouse enhancer assay, we demonstrate that one SINE locus, AS071, 178 kbp from the gene FGF8 (fibroblast growth factor 8), is an enhancer that recapitulates FGF8 expression in two regions of the developing forebrain, namely ..
  38. O Leary D, Chou S, Sahara S. Area patterning of the mammalian cortex. Neuron. 2007;56:252-69 pubmed
    ..They also interact to modify their expression, as well as expression of Fgf8. We review these mechanisms of arealization and discuss models and concepts of cortical area patterning. ..
  39. Vermot J, Gallego Llamas J, Fraulob V, Niederreither K, Chambon P, Dolle P. Retinoic acid controls the bilateral symmetry of somite formation in the mouse embryo. Science. 2005;308:563-6 pubmed
    ..These data implicate retinoic acid as an endogenous signal that maintains the bilateral synchrony of mesoderm segmentation, and therefore controls bilateral symmetry, in vertebrate embryos. ..
  40. Heer R, Douglas D, Mathers M, Robson C, Leung H. Fibroblast growth factor 17 is over-expressed in human prostate cancer. J Pathol. 2004;204:578-86 pubmed
    Over-expression of fibroblast growth factor 8 (FGF8) in human prostate cancer is associated with clinically aggressive disease...
  41. Olsen S, Li J, Bromleigh C, Eliseenkova A, Ibrahimi O, Lao Z, et al. Structural basis by which alternative splicing modulates the organizer activity of FGF8 in the brain. Genes Dev. 2006;20:185-98 pubmed
    ..Consistent with the indispensable role of FGF8 in embryonic development, we show that the FGF8 mode of receptor binding appeared as early as in nematodes and has been preserved throughout evolution. ..
  42. Suzuki A, Harada H, Nakamura H. Nuclear translocation of FGF8 and its implication to induce Sprouty2. Dev Growth Differ. 2012;54:463-73 pubmed publisher
    b>Fibroblast growth factor 8 (FGF8) functions as a local organizing signal for the tectum and cerebellum. FGF8 activates Ras-ERK signaling pathway to induce cerebellar development...
  43. Baker R, Maini P. Travelling gradients in interacting morphogen systems. Math Biosci. 2007;209:30-50 pubmed
    ..We base our model around the interactions of Fibroblast Growth Factor 8 and retinoic acid, which have been shown to act as morphogens in many developmental systems...
  44. Nilsson E, Brokken L, Narvi E, Kallio M, Harkonen P. Identification of fibroblast growth factor-8b target genes associated with early and late cell cycle events in breast cancer cells. Mol Cell Endocrinol. 2012;358:104-15 pubmed publisher
  45. Valta M, Hentunen T, Qu Q, Valve E, Harjula A, Seppänen J, et al. Regulation of osteoblast differentiation: a novel function for fibroblast growth factor 8. Endocrinology. 2006;147:2171-82 pubmed
    ..The results suggest that FGF-8, which is expressed by a great proportion of malignant breast and prostate tumors, may, among other factors, also be involved in the formation of osteosclerotic bone metastases. ..
  46. Shim K, Minowada G, Coling D, Martin G. Sprouty2, a mouse deafness gene, regulates cell fate decisions in the auditory sensory epithelium by antagonizing FGF signaling. Dev Cell. 2005;8:553-64 pubmed
    ..Our results provide evidence that antagonism of FGF signaling by SPRY2 is essential for establishing the cytoarchitecture of the organ of Corti and for hearing. ..
  47. Benadiba C, Magnani D, Niquille M, Morlé L, Valloton D, Nawabi H, et al. The ciliogenic transcription factor RFX3 regulates early midline distribution of guidepost neurons required for corpus callosum development. PLoS Genet. 2012;8:e1002606 pubmed publisher
    ..We observe focused but consistent ectopic expression of Fibroblast growth factor 8 (Fgf8) at the rostro commissural plate associated with a reduced ratio of GLIoma-associated oncogene ..
  48. Cao Y, Zhao J, Sun Z, Zhao Z, Postlethwait J, Meng A. fgf17b, a novel member of Fgf family, helps patterning zebrafish embryos. Dev Biol. 2004;271:130-43 pubmed
    ..Like fgf8, activation of fgf17b expression depends on Nodal signaling. ..
  49. Borello U, Cobos I, Long J, McWhirter J, Murre C, Rubenstein J. FGF15 promotes neurogenesis and opposes FGF8 function during neocortical development. Neural Dev. 2008;3:17 pubmed publisher
    ..FGF15 and FGF8 have distinct signaling properties, and opposite effects on neocortical patterning and differentiation; FGF15 promotes CoupTF1 expression, represses proliferation and promotes neural differentiation. ..
  50. Blak A, Naserke T, Saarimäki Vire J, Peltopuro P, Giraldo Velasquez M, Vogt Weisenhorn D, et al. Fgfr2 and Fgfr3 are not required for patterning and maintenance of the midbrain and anterior hindbrain. Dev Biol. 2007;303:231-43 pubmed
    ..This analysis shows that the Fgfr2 and the Fgfr3 on their own are dispensable for the development of the mid-/hindbrain region. We suggest functional redundancy of Fgf receptors in the mid-/hindbrain region. ..
  51. Guo Q, Li J. Distinct functions of the major Fgf8 spliceform, Fgf8b, before and during mouse gastrulation. Development. 2007;134:2251-60 pubmed
  52. Tole S, Gutin G, Bhatnagar L, Remedios R, Hebert J. Development of midline cell types and commissural axon tracts requires Fgfr1 in the cerebrum. Dev Biol. 2006;289:141-51 pubmed
  53. Lu P, Minowada G, Martin G. Increasing Fgf4 expression in the mouse limb bud causes polysyndactyly and rescues the skeletal defects that result from loss of Fgf8 function. Development. 2006;133:33-42 pubmed
    ..These data underscore the importance of controlling the level of FGF gene expression for normal limb development. ..