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Gene Review

SFRP1  -  secreted frizzled-related protein 1

Homo sapiens

Synonyms: FRP, FRP-1, FRP1, FrzA, SARP-2, ...
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Disease relevance of SFRP1


Psychiatry related information on SFRP1

  • Paroxysmal extreme pain disorder (PEPD), previously known as familial rectal pain (FRP, OMIM 167400), is an inherited disease causing intense burning rectal, ocular, and submandibular pain and flushing [5].

High impact information on SFRP1

  • Here we show that restoration of SFRP function in colorectal cancer cells attenuates WNT signaling even in the presence of downstream mutations [6].
  • An extracellular cysteine-rich domain (CRD) at the amino terminus of Frizzled proteins binds Wnt proteins, as do homologous domains in soluble proteins-termed secreted Frizzled-related proteins-that function as antagonists of Wnt signalling [7].
  • Anti-FRP-1 mAb immunoprecipitated gp80-85, gp120 and homodimers of these peptides, and anti-FRP-2 mAb reacted with gp135 identically to the alpha 3 subunit of integrin [8].
  • Sfrp2 is known to modulate Wnt signaling, and we demonstrate that cardiomyocytes treated with secreted frizzled related protein increase cellular beta-catenin and up-regulate expression of antiapoptotic genes [9].
  • FRZB encodes secreted frizzled-related protein 3, which is a soluble antagonist of wingless (wnt) signaling [10].

Chemical compound and disease context of SFRP1


Biological context of SFRP1

  • SFRP1 methylation occurred in all BE samples and in 96% of EAC, while SFRP2 was methylated in 73% of the normal squamous esophageal mucosa samples [14].
  • The chimpanzee SFRP1 gene was identified within the NW_110515.1 genome sequence [1].
  • The GLI-binding site was identified within the human SFRP1 promoter based on bioinformatics and human intelligence [1].
  • Furthermore, transfection of the SFRP gene construct into MM cell lines lacking SFRP expression resulted in apoptosis and growth suppression [3].
  • Thus, role of sFRP as a negative regulator of Wnt signaling may have important implications in tumorigenesis, and its downregulation has been correlated with human cancers [3].

Anatomical context of SFRP1


Associations of SFRP1 with chemical compounds


Regulatory relationships of SFRP1


Other interactions of SFRP1


Analytical, diagnostic and therapeutic context of SFRP1


  1. WNT antagonist, SFRP1, is Hedgehog signaling target. Katoh, Y., Katoh, M. Int. J. Mol. Med. (2006) [Pubmed]
  2. SARPs: a family of secreted apoptosis-related proteins. Melkonyan, H.S., Chang, W.C., Shapiro, J.P., Mahadevappa, M., Fitzpatrick, P.A., Kiefer, M.C., Tomei, L.D., Umansky, S.R. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  3. Expression of the secreted frizzled-related protein gene family is downregulated in human mesothelioma. Lee, A.Y., He, B., You, L., Dadfarmay, S., Xu, Z., Mazieres, J., Mikami, I., McCormick, F., Jablons, D.M. Oncogene (2004) [Pubmed]
  4. Modulated expression of secreted frizzled-related proteins in human retinal degeneration. Jones, S.E., Jomary, C., Grist, J., Stewart, H.J., Neal, M.J. Neuroreport (2000) [Pubmed]
  5. Painful channels. Catterall, W.A., Yu, F.H. Neuron (2006) [Pubmed]
  6. Epigenetic inactivation of SFRP genes allows constitutive WNT signaling in colorectal cancer. Suzuki, H., Watkins, D.N., Jair, K.W., Schuebel, K.E., Markowitz, S.D., Chen, W.D., Pretlow, T.P., Yang, B., Akiyama, Y., Van Engeland, M., Toyota, M., Tokino, T., Hinoda, Y., Imai, K., Herman, J.G., Baylin, S.B. Nat. Genet. (2004) [Pubmed]
  7. Insights into Wnt binding and signalling from the structures of two Frizzled cysteine-rich domains. Dann, C.E., Hsieh, J.C., Rattner, A., Sharma, D., Nathans, J., Leahy, D.J. Nature (2001) [Pubmed]
  8. Molecular and biological characterization of fusion regulatory proteins (FRPs): anti-FRP mAbs induced HIV-mediated cell fusion via an integrin system. Ohta, H., Tsurudome, M., Matsumura, H., Koga, Y., Morikawa, S., Kawano, M., Kusugawa, S., Komada, H., Nishio, M., Ito, Y. EMBO J. (1994) [Pubmed]
  9. Secreted frizzled related protein 2 (Sfrp2) is the key Akt-mesenchymal stem cell-released paracrine factor mediating myocardial survival and repair. Mirotsou, M., Zhang, Z., Deb, A., Zhang, L., Gnecchi, M., Noiseux, N., Mu, H., Pachori, A., Dzau, V. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  10. Functional variants within the secreted frizzled-related protein 3 gene are associated with hip osteoarthritis in females. Loughlin, J., Dowling, B., Chapman, K., Marcelline, L., Mustafa, Z., Southam, L., Ferreira, A., Ciesielski, C., Carson, D.A., Corr, M. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  11. Aberrant methylation of secreted frizzled-related protein genes in esophageal adenocarcinoma and Barrett's esophagus. Zou, H., Molina, J.R., Harrington, J.J., Osborn, N.K., Klatt, K.K., Romero, Y., Burgart, L.J., Ahlquist, D.A. Int. J. Cancer (2005) [Pubmed]
  12. Expression of Frzb/secreted Frizzled-related protein 3, a secreted Wnt antagonist, in human androgen-independent prostate cancer PC-3 cells suppresses tumor growth and cellular invasiveness. Zi, X., Guo, Y., Simoneau, A.R., Hope, C., Xie, J., Holcombe, R.F., Hoang, B.H. Cancer Res. (2005) [Pubmed]
  13. The Wnt antagonist sFRP1 is downregulated in premalignant large bowel adenomas. Caldwell, G.M., Jones, C.E., Taniere, P., Warrack, R., Soon, Y., Matthews, G.M., Morton, D.G. Br. J. Cancer (2006) [Pubmed]
  14. Alterations of the Wnt signaling pathway during the neoplastic progression of Barrett's esophagus. Clément, G., Braunschweig, R., Pasquier, N., Bosman, F.T., Benhattar, J. Oncogene (2006) [Pubmed]
  15. Cloning and characterization of a secreted frizzled-related protein that is expressed by the retinal pigment epithelium. Chang, J.T., Esumi, N., Moore, K., Li, Y., Zhang, S., Chew, C., Goodman, B., Rattner, A., Moody, S., Stetten, G., Campochiaro, P.A., Zack, D.J. Hum. Mol. Genet. (1999) [Pubmed]
  16. Secreted frizzled-related protein 1 (SFRP1) protects fibroblasts from ceramide-induced apoptosis. Han, X., Amar, S. J. Biol. Chem. (2004) [Pubmed]
  17. WNT pathway and mammary carcinogenesis: loss of expression of candidate tumor suppressor gene SFRP1 in most invasive carcinomas except of the medullary type. Ugolini, F., Charafe-Jauffret, E., Bardou, V.J., Geneix, J., Adélaïde, J., Labat-Moleur, F., Penault-Llorca, F., Longy, M., Jacquemier, J., Birnbaum, D., Pébusque, M.J. Oncogene (2001) [Pubmed]
  18. Promoter methylation of the secreted frizzled-related protein 1 gene SFRP1 is frequent in hepatocellular carcinoma. Shih, Y.L., Shyu, R.Y., Hsieh, C.B., Lai, H.C., Liu, K.Y., Chu, T.Y., Lin, Y.W. Cancer (2006) [Pubmed]
  19. DNA methylation alterations in urothelial carcinoma. Neuhausen, A., Florl, A.R., Grimm, M.O., Schulz, W.A. Cancer Biol. Ther. (2006) [Pubmed]
  20. Purification and molecular cloning of a secreted, Frizzled-related antagonist of Wnt action. Finch, P.W., He, X., Kelley, M.J., Uren, A., Schaudies, R.P., Popescu, N.C., Rudikoff, S., Aaronson, S.A., Varmus, H.E., Rubin, J.S. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  21. Expression of fusion regulatory proteins (FRPs) on human peripheral blood monocytes. Induction of homotypic cell aggregation and formation of multinucleated giant cells by anti-FRP-1 monoclonal antibodies. Tabata, N., Ito, M., Shimokata, K., Suga, S., Ohgimoto, S., Tsurudome, M., Kawano, M., Matsumura, H., Komada, H., Nishio, M. J. Immunol. (1994) [Pubmed]
  22. Functional and biochemical interactions of Wnts with FrzA, a secreted Wnt antagonist. Xu, Q., D'Amore, P.A., Sokol, S.Y. Development (1998) [Pubmed]
  23. Transcriptional silencing of secreted frizzled related protein 1 (SFRP 1) by promoter hypermethylation in non-small-cell lung cancer. Fukui, T., Kondo, M., Ito, G., Maeda, O., Sato, N., Yoshioka, H., Yokoi, K., Ueda, Y., Shimokata, K., Sekido, Y. Oncogene (2005) [Pubmed]
  24. Bone morphogenetic protein-2 modulates Wnt and frizzled expression and enhances the canonical pathway of Wnt signaling in normal keratinocytes. Yang, L., Yamasaki, K., Shirakata, Y., Dai, X., Tokumaru, S., Yahata, Y., Tohyama, M., Hanakawa, Y., Sayama, K., Hashimoto, K. J. Dermatol. Sci. (2006) [Pubmed]
  25. Differential expression of WNTs and FRPs in the synovium of rheumatoid arthritis and osteoarthritis. Imai, K., Morikawa, M., D'Armiento, J., Matsumoto, H., Komiya, K., Okada, Y. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  26. CpG island methylation and expression of the secreted frizzled-related protein gene family in chronic lymphocytic leukemia. Liu, T.H., Raval, A., Chen, S.S., Matkovic, J.J., Byrd, J.C., Plass, C. Cancer Res. (2006) [Pubmed]
  27. Methylation of APC, TIMP3, and TERT: a new predictive marker to distinguish Barrett's oesophagus patients at risk for malignant transformation. Clément, G., Braunschweig, R., Pasquier, N., Bosman, F.T., Benhattar, J. J. Pathol. (2006) [Pubmed]
  28. Secreted frizzled-related protein 1 modulates glucocorticoid attenuation of osteogenic activities and bone mass. Wang, F.S., Lin, C.L., Chen, Y.J., Wang, C.J., Yang, K.D., Huang, Y.T., Sun, Y.C., Huang, H.C. Endocrinology (2005) [Pubmed]
  29. Suppressing Wnt Signaling by the Hedgehog Pathway through sFRP-1. He, J., Sheng, T., Stelter, A.A., Li, C., Zhang, X., Sinha, M., Luxon, B.A., Xie, J. J. Biol. Chem. (2006) [Pubmed]
  30. Aberrant methylation of secreted apoptosis-related protein 2 (SARP2) in pure pancreatic juice in diagnosis of pancreatic neoplasms. Watanabe, H., Okada, G., Ohtsubo, K., Yao, F., Jiang, P.H., Mouri, H., Wakabayashi, T., Sawabu, N. Pancreas (2006) [Pubmed]
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