Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Expression of Dickkopf genes is strongly reduced in malignant melanoma


The Dickkopf (DKK) genes were originally identified as factors inducing head formation in Xenopus. The genes code for inhibitors that are involved in Wnt signaling. We speculate that loss of DKK expression plays a role in development or progression of malignant melanoma. Thus, we evaluated melanoma cell lines and tissue samples of malignant melanoma for loss of DKK, especially DKK-3 transcription. We found that DKK-1, -2 and -3 were downregulated or lost in all cell lines and in most of the tumor samples analysed. Reduced DKK-3 expression occurred as early as in primary tumors detected by both immunohistochemical and reverse transcription–polymerase chain reaction RT–PCR analysis. Functional assays with stable DKK-3 transfected cell lines revealed that DKK-3 expression increased cell-cell adhesion and decreased cell migration. Further, downregulation of fibronectin, snail-1 and re-expression of E-cadherin was found in the DKK-3 expressing cell clones supporting a role of DKK-3 in tumor progression. Our studies thus indicate that loss of DKK-3 expression may contribute to melanoma progression.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type



Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7


  • Bachelder RE, Yoon SO, Franci C, de Herreros AG, Mercurio AM . (2005). J Cell Biol 168: 29–33.

  • Behrmann I, Wallner S, Komyod W, Heinrich PC, Schuierer M, Buettner R et al. (2003). Am J Pathol 163: 683–690.

  • Berking C, Takemoto R, Satyamoorthy K, Shirakawa T, Eskandarpour M, Hansson J et al. (2004). Cancer Res 64: 807–811.

  • Bittner M, Meltzer P, Chen Y, Jiang Y, Seftor E, Hendrix M et al. (2000). Nature 406: 536–540.

  • Bogenrieder T, Herlyn M . (2003). Oncogene 22: 6524–6536.

  • De Langhe SP, Sala FG, Del Moral PM, Fairbanks TJ, Yamada KM, Warburton D et al. (2005). Dev Biol 277: 316–331.

  • Gilles C, Polette M, Birembaut P, Brunner N, Thompson EW . (1997a). Clin Exp Metastasis 15: 519–526.

  • Gilles C, Polette M, Coraux C, Tournier JM, Meneguzzi G, Munaut C et al. (2001). J Cell Sci 114: 2967–2976.

  • Gilles C, Polette M, Mestdagt M, Nawrocki-Raby B, Ruggeri P, Birembaut P et al. (2003). Cancer Res 63: 2658–2664.

  • Gilles C, Polette M, Seiki M, Birembaut P, Thompson EW . (1997b). Lab Invest 76: 651–660.

  • Gonzalez-Sancho JM, Aguilera O, Garcia JM, Pendas-Franco N, Pena C, Cal S et al. (2005). Oncogene 24: 1098–1103.

  • Haass NK, Smalley KS, Herlyn M . (2004). J Mol Histol 35: 309–318.

  • Hsieh SY, Hsieh PS, Chiu CT, Chen WY . (2004). Oncogene 23: 9183–9189.

  • Hoang BH, Kubo T, Healey JH, Yang R, Nathan SS, Kolb EA et al. (2004). Cancer Res 64: 2734–2739.

  • Jacob K, Wach F, Holzapfel U, Hein R, Lengyel E, Buettner R et al. (1998). Melanoma Res 8: 211–219.

  • Kobayashi K, Ouchida M, Tsuji T, Hanafusa H, Miyazaki M, Namba M et al. (2002). Gene 282: 151–158.

  • Krupnik VE, Sharp JD, Jiang C, Robison K, Chickering TW, Amaravadi L et al. (1999). Gene 238: 301–313.

  • Laux H, Tomer R, Mader MT, Smida J, Budczies J, Kappler R et al. (2004). Lab Invest 84: 1372–1386.

  • Lee AY, He B, You L, Xu Z, Mazieres J, Reguart N et al. (2004). Biochem Biophys Res Commun 323: 1246–1250.

  • Li G, Fukunaga M, Herlyn M . (2004). Exp Cell Res 297: 142–151.

  • Monaghan AP, Kioschis P, Wu W, Zuniga A, Bock D, Poustka A et al. (1999). Mech Dev 87: 45–56.

  • Pham K, Milovanovic T, Barr RJ, Truong T, Holcombe RF . (2003). Mol Pathol 56: 280–285.

  • Pla P, Moore R, Morali OG, Grille S, Martinozzi S, Delmas V et al. (2001). J Cell Physiol 189: 121–132.

  • Poser I, Dominguez D, de Herreros AG, Varnai A, Buettner R, Bosserhoff AK . (2001). J Biol Chem 276: 24661–24666.

  • Roman-Gomez J, Jimenez-Velasco A, Agirre X, Castillejo JA, Navarro G, Barrios M et al. (2004). Br J Cancer 91: 707–713.

  • Tester AM, Ruangpanit N, Anderson RL, Thompson EW . (2000). Clin Exp Metastasis 18: 553–560.

  • Tsuji T, Miyazaki M, Sakaguchi M, Inoue Y, Namba M . (2000). Biochem Biophys Res Commun 268: 20–24.

  • Weeraratna AT, Jiang Y, Hostetter G, Rosenblatt K, Duray P, Bittner M et al. (2002). Cancer Cell 1: 279–288.

  • Yamaguchi Y, Itami S, Watabe H, Yasumoto K, Abdel-Malek ZA, Kubo T et al. (2004). J Cell Biol 165: 275–285.

  • Yook JI, Li XY, Ota I, Fearon ER, Weiss SJ . (2005). J Biol Chem 280: 11740–11748.

  • Ziegler-Heitbrock HW, Munker R, Johnson J, Petersmann I, Schmoeckel C, Riethmuller G . (1985). Cancer Res 45: 1344–1350.

Download references


We are indebted to Dr J Johnson (University of Munich, Germany) for providing melanoma cell lines and to Susanne Wallner for excellent technical assistance. This work was supported in part by grants from the DFG and the Deutsche Krebshilfe to AB

Author information

Authors and Affiliations


Corresponding author

Correspondence to A K Bosserhoff.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Kuphal, S., Lodermeyer, S., Bataille, F. et al. Expression of Dickkopf genes is strongly reduced in malignant melanoma. Oncogene 25, 5027–5036 (2006).

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


This article is cited by


Quick links