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Gene Review

SFRP2  -  secreted frizzled-related protein 2

Homo sapiens

Synonyms: FKSG12, FRP-2, FRP2, SARP-1, SARP1, ...
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Disease relevance of SFRP2

  • SFRP2 methylation is a sensitive single DNA-based marker for the fecal screening of colorectal cancer [1].
  • Human breast adenocarcinoma MCF7 cells stably transfected with sarp1 or infected with SARP1-expressing adenovirus became more resistant, whereas cells transfected with sarp2 displayed increased sensitivity to different proapoptotic stimuli [2].
  • The expression and dysregulation of sFRP-2 in fat and obesity also suggest a potential roles on the Wnt signaling pathway in the pathology of obesity and related metabolic diseases [3].
  • These findings reveal the key role played by Sfrp2 in mediating the paracrine effects of Akt-mesenchymal stem cells on tissue repair and identify modulation of Wnt signaling as a therapeutic target for heart disease [4].
  • The downregulation of sFRP2, 4 and 5 was more frequent in carcinoma than in adenoma [5].

High impact information on SFRP2


Biological context of SFRP2


Anatomical context of SFRP2

  • 3. Based on the biology and complementary expression patterns of SFRP2 and SFRP5, we suggest that they may be involved in determining the polarity of photoreceptor, and perhaps other, cells in the retina [7].
  • Together, our results support the model that SHH-N at least in part employs SFRP2 to reduce WNT1/4 activity in the somitic mesoderm [10].
  • Thus, to elucidate the role of SFRP2 in mammary tumorigenesis, we overexpressed SFRP2 in mammary gland tumor and MCF7 cells [11].
  • Moreover, SFRP2 was found to induce tumorous transformation in normal mammary epithelial cells and to inhibit apoptosis in a modified paracrine model [11].
  • SARP1 and/or SARP2 (92-95 kDa) are ubiquitously expressed in all tissues with high levels in testis and sperm, where they are shown to interact with both PP1gamma1 and PP1gamma2 [12].

Associations of SFRP2 with chemical compounds

  • Further, estrogen-induced inhibition of adenogenesis may be mediated by a reduction in WNT signaling caused by aberrant induction of SFRP2 and loss of several critical WNTs [13].
  • The cysteine-rich domain of sFRP-2 binds to Wnt-4 as shown by coimmunoprecipitation experiments [14].
  • Wnt-4 acts in an autocrine loop to stimulate its own synthesis and is required for cells to differentiate into epithelia; its action is antagonized by sFRP-1, secreted by stroma, but this antagonism is itself inhibited by sFRP-2 made by the developing nephron [15].
  • Of those agents tested, TAM appears to be the most and Sarp A the least effective [16].

Regulatory relationships of SFRP2

  • We further show that SFRP2-expressing cells can reduce the dermomyotome-inducing activity of WNT1 and WNT4, but not that of WNT3a [10].
  • In contrast, genes encoding SARP1 and various cell cycle regulators were down-regulated in the RA synovium relative to OA [17].

Other interactions of SFRP2

  • Expression of SFRP2 and SFRP4 proteins was lower in cancers with corresponding gene methylation (p < 0.05) [18].
  • The results indicated that SFRP2 is secreted and incorporated into the extracellular matrix (ECM) of the tumor and normal cells [11].
  • SARP3 (65 kDa) is most abundant in brain where SARP isoforms interact with both PP1alpha and PP1gamma1 [12].
  • In the present paper we report the cloning and characterization of a new protein, termed SARP (several ankyrin repeat protein), which is shown to interact with all isoforms of PP1 by a variety of techniques [12].
  • DKK 1, 3, and 4 as well as sFRP 1, 4, and 5 were expressed in the exocrine fraction. sFRP 2 and 3 were detectable but only at low levels [19].

Analytical, diagnostic and therapeutic context of SFRP2


  1. Comparative genomics on SFRP2 orthologs. Katoh, M., Katoh, M. Oncol. Rep. (2005) [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. Tissue restricted expression of two human Frzbs in preadipocytes and pancreas. Hu, E., Zhu, Y., Fredrickson, T., Barnes, M., Kelsell, D., Beeley, L., Brooks, D. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  4. 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]
  5. Hypermethylation and expression regulation of secreted frizzled-related protein genes in colorectal tumor. Qi, J., Zhu, Y.Q., Luo, J., Tao, W.H. World J. Gastroenterol. (2006) [Pubmed]
  6. Myeloma cells suppress bone formation by secreting a soluble Wnt inhibitor, sFRP-2. Oshima, T., Abe, M., Asano, J., Hara, T., Kitazoe, K., Sekimoto, E., Tanaka, Y., Shibata, H., Hashimoto, T., Ozaki, S., Kido, S., Inoue, D., Matsumoto, T. Blood (2005) [Pubmed]
  7. 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]
  8. Wnt signalling regulates myogenic differentiation in the developing avian wing. Anakwe, K., Robson, L., Hadley, J., Buxton, P., Church, V., Allen, S., Hartmann, C., Harfe, B., Nohno, T., Brown, A.M., Evans, D.J., Francis-West, P. Development (2003) [Pubmed]
  9. 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]
  10. SHH-N upregulates Sfrp2 to mediate its competitive interaction with WNT1 and WNT4 in the somitic mesoderm. Lee, C.S., Buttitta, L.A., May, N.R., Kispert, A., Fan, C.M. Development (2000) [Pubmed]
  11. Autocrine/paracrine secreted Frizzled-related protein 2 induces cellular resistance to apoptosis: a possible mechanism of mammary tumorigenesis. Lee, J.L., Lin, C.T., Chueh, L.L., Chang, C.J. J. Biol. Chem. (2004) [Pubmed]
  12. SARP, a new alternatively spliced protein phosphatase 1 and DNA interacting protein. Browne, G.J., Fardilha, M., Oxenham, S.K., Wu, W., Helps, N.R., da Cruz E Silva, O.A., Cohen, P.T., da Cruz E Silva, E.F. Biochem. J. (2007) [Pubmed]
  13. WNT pathways in the neonatal ovine uterus: potential specification of endometrial gland morphogenesis by SFRP2. Hayashi, K., Spencer, T.E. Biol. Reprod. (2006) [Pubmed]
  14. sFRP-2 is a target of the Wnt-4 signaling pathway in the developing metanephric kidney. Lescher, B., Haenig, B., Kispert, A. Dev. Dyn. (1998) [Pubmed]
  15. Genes and proteins in renal development. Davies, J.A., Fisher, C.E. Exp. Nephrol. (2002) [Pubmed]
  16. Inhibition of oxidative stress in HeLa cells by chemopreventive agents. Bhimani, R.S., Troll, W., Grunberger, D., Frenkel, K. Cancer Res. (1993) [Pubmed]
  17. Regulation of GRB2 and FLICE2 expression by TNF-alpha in rheumatoid synovium. Huh, S.J., Paik, D.J., Chung, H.S., Youn, J. Immunol. Lett. (2003) [Pubmed]
  18. 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]
  19. Expression of Wnt, Frizzled, sFRP, and DKK genes in adult human pancreas. Heller, R.S., Klein, T., Ling, Z., Heimberg, H., Katoh, M., Madsen, O.D., Serup, P. Gene Expr. (2003) [Pubmed]
  20. Altered expression of secreted frizzled-related protein-2 in retinitis pigmentosa retinas. Jones, S.E., Jomary, C., Grist, J., Stewart, H.J., Neal, M.J. Invest. Ophthalmol. Vis. Sci. (2000) [Pubmed]
  21. Secreted frizzled-related protein 2 (SFRP2) is highly expressed in canine mammary gland tumors but not in normal mammary glands. Lee, J.L., Chang, C.J., Wu, S.Y., Sargan, D.R., Lin, C.T. Breast Cancer Res. Treat. (2004) [Pubmed]
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