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Gene Review

DKK3  -  dickkopf WNT signaling pathway inhibitor 3

Homo sapiens

Synonyms: Dickkopf-3, Dickkopf-related protein 3, Dkk-3, REIC, RIG, ...
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Disease relevance of DKK3

  • In order to study direct effects of these proteins on adrenocortical cell function, we created adenoviruses encoding human DKK3 and WNT4 [1].
  • Dickkopf 3 inhibits invasion and motility of Saos-2 osteosarcoma cells by modulating the Wnt-beta-catenin pathway [2].
  • Our studies thus indicate that loss of DKK-3 expression may contribute to melanoma progression [3].
  • Dkk-3/REIC was downregulated in 11 out of the 20 human hepatoma tissues as compared to their counterparts of noncancerous liver tissues by northern blot analysis [4].
  • Similarly, the REIC gene expression was decreased in 14 of 24 fresh non-small cell lung cancer specimens (58%) compared to that in corresponding non-cancerous tissue, though allelic loss and tumor-specific mutation were rare [5].
  • Our demonstration of the mechanisms underlying REIC/Dkk-3-induced cell death indicates that REIC/Dkk-3 plays a pivotal role in the biology of human malignant glioma and suggests that REIC/Dkk-3 is a promising candidate for molecular target therapy [6].

High impact information on DKK3


Biological context of DKK3


Anatomical context of DKK3


Associations of DKK3 with chemical compounds


Other interactions of DKK3

  • The higher level of DKK3 and WNT4 expression in ZF/ZG cells was confirmed by real-time PCR [11].
  • Dickkopf (Dkk) genes comprise an evolutionary conserved small gene family of four members (Dkk1-4) and a unique Dkk3-related gene, Dkkl1 (soggy) [13].
  • Dkk3 and Dkk2 expression was also concentrated at crypt bases [12].
  • We analysed CpG island methylation of the Dkk-3 promoter in six ALL cell lines and 183 ALL patients [14].
  • Injection of an IL-7 antibody partially abrogated the suppressive effect of Ad-REIC-infected NHF [15].

Analytical, diagnostic and therapeutic context of DKK3


  1. Adenovirus-delivered DKK3/WNT4 and Steroidogenesis in Primary Cultures of Adrenocortical Cells. Chen, M., Hornsby, P.J. Horm. Metab. Res. (2006) [Pubmed]
  2. Dickkopf 3 inhibits invasion and motility of Saos-2 osteosarcoma cells by modulating the Wnt-beta-catenin pathway. Hoang, B.H., Kubo, T., Healey, J.H., Yang, R., Nathan, S.S., Kolb, E.A., Mazza, B., Meyers, P.A., Gorlick, R. Cancer Res. (2004) [Pubmed]
  3. Expression of Dickkopf genes is strongly reduced in malignant melanoma. Kuphal, S., Lodermeyer, S., Bataille, F., Schuierer, M., Hoang, B.H., Bosserhoff, A.K. Oncogene (2006) [Pubmed]
  4. Dickkopf-3/REIC functions as a suppressor gene of tumor growth. Hsieh, S.Y., Hsieh, P.S., Chiu, C.T., Chen, W.Y. Oncogene (2004) [Pubmed]
  5. Reduced expression of the REIC/Dkk-3 gene by promoter-hypermethylation in human tumor cells. Kobayashi, K., Ouchida, M., Tsuji, T., Hanafusa, H., Miyazaki, M., Namba, M., Shimizu, N., Shimizu, K. Gene (2002) [Pubmed]
  6. REIC/Dkk-3 induces cell death in human malignant glioma. Mizobuchi, Y., Matsuzaki, K., Kuwayama, K., Kitazato, K., Mure, H., Kageji, T., Nagahiro, S. Neuro-oncology (2008) [Pubmed]
  7. Mesenchymal-epithelial interactions in the skin: increased expression of dickkopf1 by palmoplantar fibroblasts inhibits melanocyte growth and differentiation. Yamaguchi, Y., Itami, S., Watabe, H., Yasumoto, K., Abdel-Malek, Z.A., Kubo, T., Rouzaud, F., Tanemura, A., Yoshikawa, K., Hearing, V.J. J. Cell Biol. (2004) [Pubmed]
  8. Functional epigenomics identifies genes frequently silenced in prostate cancer. Lodygin, D., Epanchintsev, A., Menssen, A., Diebold, J., Hermeking, H. Cancer Res. (2005) [Pubmed]
  9. Adenovirus-mediated overexpression of REIC/Dkk-3 selectively induces apoptosis in human prostate cancer cells through activation of c-Jun-NH2-kinase. Abarzua, F., Sakaguchi, M., Takaishi, M., Nasu, Y., Kurose, K., Ebara, S., Miyazaki, M., Namba, M., Kumon, H., Huh, N.H. Cancer Res. (2005) [Pubmed]
  10. Advanced molecular profiling in vivo detects novel function of dickkopf-3 in the regulation of bone formation. Aslan, H., Ravid-Amir, O., Clancy, B.M., Rezvankhah, S., Pittman, D., Pelled, G., Turgeman, G., Zilberman, Y., Gazit, Z., Hoffmann, A., Gross, G., Domany, E., Gazit, D. J. Bone Miner. Res. (2006) [Pubmed]
  11. Zonal expression of dickkopf-3 and components of the Wnt signalling pathways in the human adrenal cortex. Suwa, T., Chen, M., Hawks, C.L., Hornsby, P.J. J. Endocrinol. (2003) [Pubmed]
  12. Expression of secreted Wnt antagonists in gastrointestinal tissues: potential role in stem cell homeostasis. Byun, T., Karimi, M., Marsh, J.L., Milovanovic, T., Lin, F., Holcombe, R.F. J. Clin. Pathol. (2005) [Pubmed]
  13. Function and biological roles of the Dickkopf family of Wnt modulators. Niehrs, C. Oncogene (2006) [Pubmed]
  14. Transcriptional silencing of the Dickkopfs-3 (Dkk-3) gene by CpG hypermethylation in acute lymphoblastic leukaemia. Roman-Gomez, J., Jimenez-Velasco, A., Agirre, X., Castillejo, J.A., Navarro, G., Barrios, M., Andreu, E.J., Prosper, F., Heiniger, A., Torres, A. Br. J. Cancer (2004) [Pubmed]
  15. Overexpression of REIC/Dkk-3 in normal fibroblasts suppresses tumor growth via induction of interleukin-7. Sakaguchi, M., Kataoka, K., Abarzua, F., Tanimoto, R., Watanabe, M., Murata, H., Than, S.S., Kurose, K., Kashiwakura, Y., Ochiai, K., Nasu, Y., Kumon, H., Huh, N.H. J. Biol. Chem. (2009) [Pubmed]
  16. Decreased expression of REIC/Dkk-3 in human renal clear cell carcinoma. Kurose, K., Sakaguchi, M., Nasu, Y., Ebara, S., Kaku, H., Kariyama, R., Arao, Y., Miyazaki, M., Tsushima, T., Namba, M., Kumon, H., Huh, N.H. J. Urol. (2004) [Pubmed]
  17. Regulation of prostate cell growth and morphogenesis by Dickkopf-3. Kawano, Y., Kitaoka, M., Hamada, Y., Walker, M.M., Waxman, J., Kypta, R.M. Oncogene (2006) [Pubmed]
  18. REIC/Dkk-3 as a potential gene therapeutic agent against human testicular cancer. Tanimoto, R., Abarzua, F., Sakaguchi, M., Takaishi, M., Nasu, Y., Kumon, H., Huh, N.H. Int. J. Mol. Med. (2007) [Pubmed]
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