FZD8

Summary

Gene Symbol: FZD8
Description: frizzled class receptor 8
Alias: FZ-8, hFZ8, frizzled-8, frizzled 8, seven transmembrane spanning receptor, frizzled family receptor 8, frizzled homolog 8
Species: human
Products:     FZD8

Top Publications

  1. Wang H, Xu M, Ma J, Zhang Y, Xie C. Frizzled-8 as a putative therapeutic target in human lung cancer. Biochem Biophys Res Commun. 2012;417:62-6 pubmed publisher
    ..These data suggest that Fzd-8 is a putative therapeutic target for human lung cancer and over-expression of Fzd-8 may be important for aberrant Wnt activation in lung cancer. ..
  2. Tamai K, Semenov M, Kato Y, Spokony R, Liu C, Katsuyama Y, et al. LDL-receptor-related proteins in Wnt signal transduction. Nature. 2000;407:530-5 pubmed
    ..The extracellular domain of LRP6 bound Wnt-1 and associated with Fz in a Wnt-dependent manner. Our results indicate that LRP6 may be a component of the Wnt receptor complex. ..
  3. Semenov M, Tamai K, Brott B, Kuhl M, Sokol S, He X. Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6. Curr Biol. 2001;11:951-61 pubmed
    ..Our findings suggest that Wnt-Fz-LRP6 complex formation, but not Wnt-Fz interaction, triggers Wnt/beta-catenin signaling. ..
  4. Dann C, Hsieh J, Rattner A, Sharma D, Nathans J, Leahy D. Insights into Wnt binding and signalling from the structures of two Frizzled cysteine-rich domains. Nature. 2001;412:86-90 pubmed
    ..the molecular nature of the Wnt signalling complex, we determined the crystal structures of the CRDs from mouse Frizzled 8 and secreted Frizzled-related protein 3...
  5. Kaur M, Hartling I, Burnett T, Polsky L, Donnan C, Leclerc H, et al. Rumen-protected B vitamin complex supplementation during the transition period and early lactation alters endometrium mRNA expression on day 14 of gestation in lactating dairy cows. J Dairy Sci. 2019;102:1642-1657 pubmed publisher
    ..immune system, adhesion, and regulation of vitamin B molecules showed that OXTR, MUC5B, MUC1, IL1B, SPP, TRD, FZD8, and FOLR1 genes were significantly upregulated in the VB group...
  6. Frost J, Estivill X, Ramsay M, Tikly M. Dysregulation of the Wnt signaling pathway in South African patients with diffuse systemic sclerosis. Clin Rheumatol. 2019;38:933-938 pubmed publisher
    ..These included the Wnt ligands WNT7A and WNT10A, the frizzled receptors FZD8 and FZD9, intracellular signaling proteins AXIN1 and AXIN2, and the pathway target genes FGF4 and MMP7...
  7. Crow K, Smith C, Cheng J, Wagner G, Amemiya C. An independent genome duplication inferred from Hox paralogs in the American paddlefish--a representative basal ray-finned fish and important comparative reference. Genome Biol Evol. 2012;4:937-53 pubmed publisher
    ..We also provide a gene genealogy for the duplicated fzd8 gene in paddlefish and present evidence for the first Hox14 gene in any ray-finned fish...
  8. Benson M, Khor C, Gage P, Lehmann O. A targeted approach to genome-wide studies reveals new genetic associations with central corneal thickness. Mol Vis. 2017;23:952-962 pubmed
    ..12×10-3 and rs4854785, p=1.11×10-3), and FZD8 (rs640827, p=5.17×10-4) were statistically significantly associated with CCT...
  9. Hughes K, Sablitzky F, Mahida Y. Expression profiling of Wnt family of genes in normal and inflammatory bowel disease primary human intestinal myofibroblasts and normal human colonic crypt epithelial cells. Inflamm Bowel Dis. 2011;17:213-20 pubmed publisher
    ..Most of the myofibroblast isolates expressed Wnt2, Wnt5A, Wnt5B, Fzd1, Fzd2, Fzd4, Fzd6, Fzd7, Fzd8, LRP6, Dickkopf1, and SFRP1...

More Information

Publications58

  1. Janda C, Garcia K. Wnt acylation and its functional implication in Wnt signalling regulation. Biochem Soc Trans. 2015;43:211-6 pubmed publisher
    ..Intriguingly, the crystal structure of XWnt8 in complex with the extracellular domain of the Frizzled 8 cysteine-rich domain (Fzd8-CRD) revealed that Wnts use the fatty acid as a 'hotspot' residue to engage its ..
  2. Miao C, Shi W, Xiong Y, Yu H, Zhang X, Qin M, et al. miR-375 regulates the canonical Wnt pathway through FZD8 silencing in arthritis synovial fibroblasts. Immunol Lett. 2015;164:1-10 pubmed publisher
    ..Because the web-based software TargetScan and PicTar predict Frizzled 8 (FZD8) as the target of miR-375, we investigated whether up-regulated miR-375 plays a role in the activation of ..
  3. Le P, McDermott J, Jimeno A. Targeting the Wnt pathway in human cancers: therapeutic targeting with a focus on OMP-54F28. Pharmacol Ther. 2015;146:1-11 pubmed publisher
    ..OMP-54F28 is a fusion protein that combines the cysteine-rich domain of frizzled family receptor 8 (Fzd8) with the immunoglobulin Fc domain that competes with the native Fzd8 receptor for its ligands and ..
  4. Shi X, Zhu M, Kang Y, Yang T, Chen X, Zhang Y. Wnt/?-catenin signaling pathway is involved in regulating the migration by an effective natural compound brucine in LoVo cells. Phytomedicine. 2018;46:85-92 pubmed publisher
    ..Brucine could suppress the migration of the colorectal cancer in vitro and in vivo and the effect was associated with the inhibition of the Wnt/?-catenin signaling pathway. ..
  5. Nachtergaele S, Whalen D, Mydock L, Zhao Z, Malinauskas T, Krishnan K, et al. Structure and function of the Smoothened extracellular domain in vertebrate Hedgehog signaling. elife. 2013;2:e01340 pubmed publisher
    ..The oxysterol-binding groove in the Smo CRD is analogous to that used by Frizzled 8 to bind to the palmitoleyl group of Wnt ligands and to similar pockets used by other Frizzled-like CRDs to bind ..
  6. Murillo Garzón V, Gorroño Etxebarria I, Akerfelt M, Puustinen M, Sistonen L, Nees M, et al. Frizzled-8 integrates Wnt-11 and transforming growth factor-β signaling in prostate cancer. Nat Commun. 2018;9:1747 pubmed publisher
    ..b>FZD8 mRNA is upregulated in multiple prostate cancer datasets and in metastatic cancer cell lines in vitro and in vivo...
  7. Xue J, Yang J, Yang L, Zhou S, Ji C, Wang X, et al. Dickkopf-1 Is a Biomarker for Systemic Lupus Erythematosus and Active Lupus Nephritis. J Immunol Res. 2017;2017:6861575 pubmed publisher
    ..These results imply that serum and/or urine DKK-1 may be a valuable and independent biomarker for identification of SLE patients with LN. ..
  8. Jin Y, Liu Y, Zhang J, Huang W, Jiang H, Hou Y, et al. The Expression of miR-375 Is Associated with Carcinogenesis in Three Subtypes of Lung Cancer. PLoS ONE. 2015;10:e0144187 pubmed publisher
    ..Moreover, we performed dual luciferase reporter assay and Western blot on 6 targeted genes (FZD8, ITGA10, ITPKB, LRP5, PIAS1 andRUNX1) in small cell lung carcinoma cell line NCI-H82...
  9. Janda C, Dang L, You C, Chang J, de Lau W, Zhong Z, et al. Surrogate Wnt agonists that phenocopy canonical Wnt and ?-catenin signalling. Nature. 2017;545:234-237 pubmed publisher
    ..Here we develop surrogate Wnt agonists, water-soluble FZD-LRP5/LRP6 heterodimerizers, with FZD5/FZD8-specific and broadly FZD-reactive binding domains...
  10. Xu J, Feng X, Jia Y, Hong Y, Li H, Lu K, et al. Characterization and expression pattern of a novel Frizzled 8 receptor gene in Schistosoma japonicum. Parasitol Int. 2017;66:522-528 pubmed publisher
  11. Nile A, Mukund S, Stanger K, Wang W, Hannoush R. Unsaturated fatty acyl recognition by Frizzled receptors mediates dimerization upon Wnt ligand binding. Proc Natl Acad Sci U S A. 2017;114:4147-4152 pubmed publisher
    ..Re-evaluation of the published mouse FZD8 CRD structure reveals that it also shares the same architecture as FZD5 and FZD7 CRDs...
  12. Spanjer A, Baarsma H, Oostenbrink L, Jansen S, Kuipers C, Lindner M, et al. TGF-β-induced profibrotic signaling is regulated in part by the WNT receptor Frizzled-8. FASEB J. 2016;30:1823-35 pubmed publisher
    ..Specific small interfering RNA was used to knock down FZD8. In vivo studies using bleomycin-induced lung fibrosis were performed in wild-type and FZD8-deficient mice...
  13. Lu X, Wang F, Xu C, Soodvilai S, Peng K, Su J, et al. Soluble (pro)renin receptor via ?-catenin enhances urine concentration capability as a target of liver X receptor. Proc Natl Acad Sci U S A. 2016;113:E1898-906 pubmed publisher
    ..A template-based algorithm for protein-protein interaction predicted the interaction between sPRR and frizzled-8 (FZD8), which subsequently was confirmed by coimmunoprecipitation...
  14. Huang C, Xu J, Zhong W, Xia Z, Wang S, Cheng D, et al. Sox9 transcriptionally regulates Wnt signaling in intestinal epithelial stem cells in hypomethylated crypts in the diabetic state. Stem Cell Res Ther. 2017;8:60 pubmed publisher
    ..Sox9 predominantly acts as a transcriptional activator at proximal enhancers of Wnt4, Tab2, Sox4, and Fzd8, but also functions as a potential transcriptional inhibitor at a distant enhancer of Cdk1...
  15. Mebarki S, Désert R, Sulpice L, Sicard M, Desille M, Canal F, et al. De novo HAPLN1 expression hallmarks Wnt-induced stem cell and fibrogenic networks leading to aggressive human hepatocellular carcinomas. Oncotarget. 2016;7:39026-39043 pubmed publisher
    ..Invasion was inhibited by 30 nM FZD7 and FZD8 CRDs...
  16. Steinhart Z, Pavlovic Z, Chandrashekhar M, Hart T, Wang X, Zhang X, et al. Genome-wide CRISPR screens reveal a Wnt-FZD5 signaling circuit as a druggable vulnerability of RNF43-mutant pancreatic tumors. Nat Med. 2017;23:60-68 pubmed publisher
    ..Additionally, antibodies that specifically bind FZD5 and FZD8 robustly inhibited the growth of RNF43-mutant PDAC cells grown in vitro and as xenografts in vivo, providing ..
  17. Beljaars L, Daliri S, Dijkhuizen C, Poelstra K, Gosens R. WNT-5A regulates TGF-?-related activities in liver fibrosis. Am J Physiol Gastrointest Liver Physiol. 2017;312:G219-G227 pubmed publisher
    ..Additionally, TGF-? induces the expression of the WNT receptors FZD2 and FZD8. After silencing of WNT-5A, reduced levels of collagen type I, vimentin, and fibronectin in TGF-?-stimulated ..
  18. González Fernández C, Arevalo Martin A, Paniagua Torija B, Ferrer I, Rodriguez F, Garcia Ovejero D. Wnts Are Expressed in the Ependymal Region of the Adult Spinal Cord. Mol Neurobiol. 2017;54:6342-6355 pubmed publisher
    ..age on spontaneous proliferation of ependymal cells in rats paralleled by a decrease in the expression of Fzd1, Fzd8, and Fzd9...
  19. Zhou F, Xu X, Wang D, Wu J, Wang J. Identification of novel NF-?B transcriptional targets in TNF?-treated HeLa and HepG2 cells. Cell Biol Int. 2017;41:555-569 pubmed publisher
    ..Apart from the known target genes, we also found some novel PTGs including CYCS, MITF, FZD1, FZD8, and PIAS1. We subsequently demonstrated whether NF-?B transcriptionally control the five PTGs...
  20. Alok A, Lei Z, Jagannathan N, Kaur S, Harmston N, Rozen S, et al. Wnt proteins synergize to activate ?-catenin signaling. J Cell Sci. 2017;130:1532-1544 pubmed publisher
    ..WNT1- and WNT7B-mediated synergistic Wnt signaling requires FZD5, FZD8 and LRP6, as well as the WNT7B co-receptors GPR124 (also known as ADGRA2) and RECK...
  21. Chang B, Tessneer K, McManus J, Liu X, Hahn S, Pasula S, et al. Epsin is required for Dishevelled stability and Wnt signalling activation in colon cancer development. Nat Commun. 2015;6:6380 pubmed publisher
    ..The pro-carcinogenic role of Epsins suggests that they are potential therapeutic targets to combat colon cancer. ..
  22. Yang Q, Wang Y, Pan X, Ye J, Gan S, Qu F, et al. Frizzled 8 promotes the cell proliferation and metastasis of renal cell carcinoma. Oncotarget. 2017;8:78989-79002 pubmed publisher
    ..b>Frizzled 8 (FZD8) is a member of Frizzled (FZD) receptor family which could activate canonical or non-canonical Wnt/?-..
  23. Jiang Q, He M, Guan S, Ma M, Wu H, Yu Z, et al. MicroRNA-100 suppresses the migration and invasion of breast cancer cells by targeting FZD-8 and inhibiting Wnt/β-catenin signaling pathway. Tumour Biol. 2016;37:5001-11 pubmed publisher
  24. Boyd J, Skove S, Rouanet J, Pilaz L, Bepler T, Gordân R, et al. Human-chimpanzee differences in a FZD8 enhancer alter cell-cycle dynamics in the developing neocortex. Curr Biol. 2015;25:772-9 pubmed publisher
    ..Here we report the discovery of a human-accelerated regulatory enhancer (HARE5) of FZD8, a receptor of the Wnt pathway implicated in brain development and size [15, 16]...
  25. Yao R, Maeda T, Takada S, Noda T. Identification of a PDZ domain containing Golgi protein, GOPC, as an interaction partner of frizzled. Biochem Biophys Res Commun. 2001;286:771-8 pubmed
    ..Taken together, these results indicate that GOPC may play a role in the vesicle transport of frizzled from the Golgi apparatus to the plasma membrane. ..
  26. Omoto S, Hayashi T, Kitahara K, Takeuchi T, Ueoka Y. Autosomal dominant familial exudative vitreoretinopathy in two Japanese families with FZD4 mutations (H69Y and C181R). Ophthalmic Genet. 2004;25:81-90 pubmed
    ..Analysis of FZD4 mutations in families with adFEVR is useful for genetic counseling and for early diagnosis ..
  27. Kramer N, Schmöllerl J, Unger C, Nivarthi H, Rudisch A, Unterleuthner D, et al. Autocrine WNT2 signaling in fibroblasts promotes colorectal cancer progression. Oncogene. 2017;36:5460-5472 pubmed publisher
    ..We identified FZD8 as the putative WNT2 receptor in CAFs...
  28. Lyons P, Rayner T, Trivedi S, Holle J, Watts R, Jayne D, et al. Genetically distinct subsets within ANCA-associated vasculitis. N Engl J Med. 2012;367:214-23 pubmed publisher
    ..These data provide preliminary support for the concept that proteinase 3 ANCA-associated vasculitis and myeloperoxidase ANCA-associated vasculitis are distinct autoimmune syndromes. (Funded by the British Heart Foundation and others.). ..
  29. Hendaoui I, Lavergne E, Lee H, Hong S, Kim H, Parent C, et al. Inhibition of Wnt/?-catenin signaling by a soluble collagen-derived frizzled domain interacting with Wnt3a and the receptors frizzled 1 and 8. PLoS ONE. 2012;7:e30601 pubmed publisher
    ..of full-length frizzled 1 and 8 receptors, but enhanced by the expression of a chimeric cell-membrane-tethered frizzled 8 CRD. Moreover, soluble, partially purified recombinant FZC18_CRD inhibited Wnt3a-induced ?-catenin activation...
  30. Bravo D, Yang Y, Kuchenbecker K, Hung M, Xu Z, Jablons D, et al. Frizzled-8 receptor is activated by the Wnt-2 ligand in non-small cell lung cancer. BMC Cancer. 2013;13:316 pubmed publisher
    ..The dnhWnt-2 construct may provide a new therapeutic avenue for targeting the Wnt pathway in lung cancer. ..
  31. Lu W, Yamamoto V, Ortega B, Baltimore D. Mammalian Ryk is a Wnt coreceptor required for stimulation of neurite outgrowth. Cell. 2004;119:97-108 pubmed
    ..Thus, Ryk appears to play a crucial role in Wnt-mediated signaling. ..
  32. Spanjer A, Menzen M, Dijkstra A, van den Berge M, Boezen H, Nickle D, et al. A pro-inflammatory role for the Frizzled-8 receptor in chronic bronchitis. Thorax. 2016;71:312-22 pubmed publisher
    ..lung expression quantitative trait loci (eQTL) analyses for Frizzled-8 were performed to evaluate polymorphisms in FZD8 and their relationship to tissue expression in chronic bronchitis...
  33. Jimeno A, Gordon M, Chugh R, Messersmith W, Mendelson D, Dupont J, et al. A First-in-Human Phase I Study of the Anticancer Stem Cell Agent Ipafricept (OMP-54F28), a Decoy Receptor for Wnt Ligands, in Patients with Advanced Solid Tumors. Clin Cancer Res. 2017;23:7490-7497 pubmed publisher
    ..Ipafricept (OMP-54F28) is a first-in-class recombinant fusion protein with the extracellular part of human frizzled 8 receptor fused to a human IgG1 Fc fragment that binds Wnt ligands...
  34. Hamdoun S, Fleischer E, Klinger A, Efferth T. Lawsone derivatives target the Wnt/?-catenin signaling pathway in multidrug-resistant acute lymphoblastic leukemia cells. Biochem Pharmacol. 2017;146:63-73 pubmed publisher
    ..Wnt/?-catenin signaling, therefore, represents a potential therapeutic target for the selective killing of Pgp-mediated MDR. ..
  35. Li Z, Zhu Y, Yu M, Ji D, Yang Z, Kong C. c-Jun is involved in interstitial cystitis antiproliferative factor (APF)-induced growth inhibition of human bladder cancer T24 cells. Urol Oncol. 2013;31:228-33 pubmed publisher
    ..These observations suggest that c-Jun is involved in APF-mediated inhibition for bladder tumor cell growth, as potential target of APF in patients with aggressive bladder carcinoma. ..
  36. Luyten A, Mortier E, Van Campenhout C, Taelman V, Degeest G, Wuytens G, et al. The postsynaptic density 95/disc-large/zona occludens protein syntenin directly interacts with frizzled 7 and supports noncanonical Wnt signaling. Mol Biol Cell. 2008;19:1594-604 pubmed publisher
    ..We propose that syntenin is a novel component of the Wnt signal transduction cascade and that it might function as a direct intracellular link between Frizzled and syndecans. ..
  37. Hamilton P, Sun Y, Henry J. Lens regeneration from the cornea requires suppression of Wnt/β-catenin signaling. Exp Eye Res. 2016;145:206-215 pubmed publisher
    ..Numerous frizzled receptors (fzd1, fzd2, fzd3, fzd4, fzd6, fzd7, fzd8, and fzd10) and wnt ligands (wnt2b...
  38. Sun S, Liu S, Duan S, Zhang L, Zhou H, Hu Y, et al. Targeting the c-Met/FZD8 signaling axis eliminates patient-derived cancer stem-like cells in head and neck squamous carcinomas. Cancer Res. 2014;74:7546-59 pubmed publisher
    ..CSC elimination was due to downregulation of Wnt/β-catenin signaling in HN-CSC and that the Wnt pathway receptor FZD8 was essential for interactions of c-Met and Wnt/β-catenin signaling in HN-CSC...
  39. Wang M, Holderfield M, Galeas J, DelRosario R, To M, Balmain A, et al. K-Ras Promotes Tumorigenicity through Suppression of Non-canonical Wnt Signaling. Cell. 2015;163:1237-1251 pubmed publisher
    ..K-Ras does this by binding to calmodulin and so reducing CaMKii activity and expression of Fzd8. Restoring Fzd8 in K-Ras mutant pancreatic cells suppresses malignancy, whereas depletion of Fzd8 in H-Ras(V12)-..
  40. Saitoh T, Hirai M, Katoh M. Molecular cloning and characterization of human Frizzled-8 gene on chromosome 10p11.2. Int J Oncol. 2001;18:991-6 pubmed
    ..We have cloned and characterized the human Frizzled-8 (FZD8) gene, a human homologue of mouse Frizzled-8...
  41. Finch P, He X, Kelley M, Uren A, Schaudies R, Popescu N, et al. Purification and molecular cloning of a secreted, Frizzled-related antagonist of Wnt action. Proc Natl Acad Sci U S A. 1997;94:6770-5 pubmed
    ..These results indicate that FRP may function as an inhibitor of Wnt action during development and in the adult. ..
  42. Yang W, Kim Y, Kim T, Keay S, Kim K, Steen H, et al. Integration analysis of quantitative proteomics and transcriptomics data identifies potential targets of frizzled-8 protein-related antiproliferative factor in vivo. BJU Int. 2012;110:E1138-46 pubmed publisher
    ..This unbiased integration analysis of in vitro quantitative proteomics data with in vivo quantitative transcriptomics data led to the identification of potential downstream mediators of the APF signal transduction pathway. ..
  43. Hao H, Xie Y, Zhang Y, Charlat O, Oster E, Avello M, et al. ZNRF3 promotes Wnt receptor turnover in an R-spondin-sensitive manner. Nature. 2012;485:195-200 pubmed publisher
    ..These data suggest that R-spondin enhances Wnt signalling by inhibiting ZNRF3. Our study provides new mechanistic insights into the regulation of Wnt receptor turnover, and reveals ZNRF3 as a tractable target for therapeutic exploration...
  44. Voronkov A, Baskin I, Palyulin V, Zefirov N. Molecular model of the Wnt protein binding site on the surface of dimeric CRD domain of the hFzd8 receptor. Dokl Biochem Biophys. 2008;419:75-8 pubmed
  45. Li Q, Ye L, Zhang X, Wang M, Lin C, Huang S, et al. FZD8, a target of p53, promotes bone metastasis in prostate cancer by activating canonical Wnt/β-catenin signaling. Cancer Lett. 2017;402:166-176 pubmed publisher
    ..Herein, we reported that among the FZD family, FZD8 was robustly upregulated in bone-metastastic PCa cell lines and tissues...
  46. Semenov M, Tamai K, He X. SOST is a ligand for LRP5/LRP6 and a Wnt signaling inhibitor. J Biol Chem. 2005;280:26770-5 pubmed
    ..Our findings suggest that SOST is an antagonist for Wnt signaling and that the loss of SOST function likely leads to the hyperactivation of Wnt signaling that underlies bone overgrowth seen in sclerosteosis patients. ..
  47. Xu L, Wen T, Liu Z, Xu F, Yang L, Liu J, et al. MicroRNA-375 suppresses human colorectal cancer metastasis by targeting Frizzled 8. Oncotarget. 2016;7:40644-40656 pubmed publisher
    ..Furthermore, we identified Frizzled 8 (FZD8) as a direct target of miR-375 in CRC, and miR-375 negatively regulated Wnt/?-catenin signaling by ..
  48. Naito A, Sumida T, Nomura S, Liu M, Higo T, Nakagawa A, et al. Complement C1q activates canonical Wnt signaling and promotes aging-related phenotypes. Cell. 2012;149:1298-313 pubmed publisher
    ..Our findings therefore suggest the unexpected role of complement C1q in Wnt signal transduction and modulation of mammalian aging. ..
  49. Bourhis E, Tam C, Franke Y, Bazan J, Ernst J, Hwang J, et al. Reconstitution of a frizzled8.Wnt3a.LRP6 signaling complex reveals multiple Wnt and Dkk1 binding sites on LRP6. J Biol Chem. 2010;285:9172-9 pubmed publisher
    ..The existence of multiple, independent Wnt binding sites on the LRP6 co-receptor suggests new possibilities for the architecture of Wnt signaling complexes and a model for broad-spectrum inhibition of Wnt/beta-catenin signaling by Dkk1. ..