DKK1

Summary

Gene Symbol: DKK1
Description: dickkopf WNT signaling pathway inhibitor 1
Alias: DKK-1, dickkopf-related protein 1, dickkopf 1 homolog, dickkopf-1 like, dickkopf-like protein 1
Species: human
Products:     DKK1

Top Publications

  1. Aguilera O, Fraga M, Ballestar E, Paz M, Herranz M, Espada J, et al. Epigenetic inactivation of the Wnt antagonist DICKKOPF-1 (DKK-1) gene in human colorectal cancer. Oncogene. 2006;25:4116-21 pubmed
  2. Hall C, Zhang H, Baile S, Ljungman M, Kuhstoss S, Keller E. p21CIP-1/WAF-1 induction is required to inhibit prostate cancer growth elicited by deficient expression of the Wnt inhibitor Dickkopf-1. Cancer Res. 2010;70:9916-26 pubmed publisher
    ..Collectively, our findings demonstrate that DKK-1 overexpression supports tumor growth in part by restricting expression of p21(CIP1/WAF1) through a mechanism independent of canonical Wnt signaling. ..
  3. Yaccoby S, Ling W, Zhan F, Walker R, Barlogie B, Shaughnessy J. Antibody-based inhibition of DKK1 suppresses tumor-induced bone resorption and multiple myeloma growth in vivo. Blood. 2007;109:2106-11 pubmed
    Dickkopf-1 (DKK1), a soluble inhibitor of Wnt signaling secreted by multiple myeloma (MM) cells contributes to osteolytic bone disease by inhibiting the differentiation of osteoblasts...
  4. Qiang Y, Chen Y, Stephens O, Brown N, Chen B, Epstein J, et al. Myeloma-derived Dickkopf-1 disrupts Wnt-regulated osteoprotegerin and RANKL production by osteoblasts: a potential mechanism underlying osteolytic bone lesions in multiple myeloma. Blood. 2008;112:196-207 pubmed publisher
    ..We demonstrate here that MM cell-derived DKK1, a soluble inhibitor of canonical Wnt signaling, disrupted Wnt3a-regulated OPG and RANKL expression in osteoblasts...
  5. Fedi P, Bafico A, Nieto Soria A, Burgess W, Miki T, Bottaro D, et al. Isolation and biochemical characterization of the human Dkk-1 homologue, a novel inhibitor of mammalian Wnt signaling. J Biol Chem. 1999;274:19465-72 pubmed
    ..These results provide biochemical evidence that human Sk/Dkk-1 antagonizes Wnt signaling upstream of its effect on beta-catenin regulation. ..
  6. Shou J, Ali Osman F, Multani A, Pathak S, Fedi P, Srivenugopal K. Human Dkk-1, a gene encoding a Wnt antagonist, responds to DNA damage and its overexpression sensitizes brain tumor cells to apoptosis following alkylation damage of DNA. Oncogene. 2002;21:878-89 pubmed
    ..These results show that hDkk-1 is a pro-apoptotic gene and suggest that it may play important roles in linking the oncogenic Wnt and p53 tumor suppressor pathways. ..
  7. Gustafson B, Eliasson B, Smith U. Thiazolidinediones increase the wingless-type MMTV integration site family (WNT) inhibitor Dickkopf-1 in adipocytes: a link with osteogenesis. Diabetologia. 2010;53:536-40 pubmed publisher
    Dickkopf-1 (DKK1) is a secreted inhibitor of canonical wingless-type MMTV integration site family (WNT) signalling; the key pathway for cell fate and development...
  8. González Sancho J, Aguilera O, Garcia J, Pendás Franco N, Peña C, Cal S, et al. The Wnt antagonist DICKKOPF-1 gene is a downstream target of beta-catenin/TCF and is downregulated in human colon cancer. Oncogene. 2005;24:1098-103 pubmed
    ..Our data indicate that the Wnt/beta-catenin pathway is downregulated by the induction of DKK-1 expression, a mechanism that is lost in colon cancer. ..
  9. Koch S, Capaldo C, Samarin S, Nava P, Neumaier I, Skerra A, et al. Dkk-1 inhibits intestinal epithelial cell migration by attenuating directional polarization of leading edge cells. Mol Biol Cell. 2009;20:4816-25 pubmed publisher
    ..Together, these data demonstrate a novel role of Dkk-1 in the regulation of directional polarization of migrating intestinal epithelial cells, which contributes to the effect of Dkk-1 on wound closure in vivo. ..

More Information

Publications101 found, 100 shown here

  1. Jiang T, Huang L, Zhang S. DKK-1 in serum as a clinical and prognostic factor in patients with cervical cancer. Int J Biol Markers. 2013;28:221-5 pubmed publisher
    ..Because DKK-1 is a secreted protein, we investigated whether it could be found in the serum of patients with cervical cancer...
  2. Forget M, Turcotte S, Beauseigle D, Godin Ethier J, Pelletier S, Martin J, et al. The Wnt pathway regulator DKK1 is preferentially expressed in hormone-resistant breast tumours and in some common cancer types. Br J Cancer. 2007;96:646-53 pubmed
    ..In this study, we report the expression of Dickkopf-1 (DKK1) in multiple common cancers. This constitutes a comprehensive analysis of the DKK1 expression profile...
  3. Gregory C, Singh H, Perry A, Prockop D. The Wnt signaling inhibitor dickkopf-1 is required for reentry into the cell cycle of human adult stem cells from bone marrow. J Biol Chem. 2003;278:28067-78 pubmed
    ..Since antibodies to Dkk-1 also increased the lag phase of an osteosarcoma line that expressed the gene, Dkk-1 may have a similar role in some other cell systems. ..
  4. Sakane H, Yamamoto H, Michiue T, Kikuchi A. Wnt3a and Dkk1 regulate distinct internalization pathways of LRP6 to tune the activation of beta-catenin signaling. Dev Cell. 2008;15:37-48 pubmed publisher
    ..In contrast, Dkk1, which inhibits Wnt3a-dependent stabilization of beta-catenin, induced the internalization of LRP6 with clathrin...
  5. Lee N, Smolarz A, Olson S, David O, Reiser J, Kutner R, et al. A potential role for Dkk-1 in the pathogenesis of osteosarcoma predicts novel diagnostic and treatment strategies. Br J Cancer. 2007;97:1552-9 pubmed
  6. Thambiah S, Roplekar R, Manghat P, Fogelman I, Fraser W, Goldsmith D, et al. Circulating sclerostin and Dickkopf-1 (DKK1) in predialysis chronic kidney disease (CKD): relationship with bone density and arterial stiffness. Calcif Tissue Int. 2012;90:473-80 pubmed publisher
    ..was to investigate the possible association of circulating concentrations of the secreted Wnt signaling inhibitors DKK1 and sclerostin with BMD and arterial stiffness in predialysis CKD...
  7. Mao B, Wu W, Li Y, Hoppe D, Stannek P, Glinka A, et al. LDL-receptor-related protein 6 is a receptor for Dickkopf proteins. Nature. 2001;411:321-5 pubmed
    ..Wnt signalling is antagonized by the extracellular Wnt inhibitor dickkopf1 (dkk1), which is a member of a multigene family...
  8. Binnerts M, Kim K, Bright J, Patel S, Tran K, Zhou M, et al. R-Spondin1 regulates Wnt signaling by inhibiting internalization of LRP6. Proc Natl Acad Sci U S A. 2007;104:14700-5 pubmed
    ..Although RSpo1 does not directly activate LRP6, it interferes with DKK1/Kremen-mediated internalization of LRP6 through an interaction with Kremen, resulting in increased LRP6 levels on ..
  9. Bafico A, Liu G, Yaniv A, Gazit A, Aaronson S. Novel mechanism of Wnt signalling inhibition mediated by Dickkopf-1 interaction with LRP6/Arrow. Nat Cell Biol. 2001;3:683-6 pubmed
  10. Park J, Jung J, Lee Y, Kang K. The roles of Wnt antagonists Dkk1 and sFRP4 during adipogenesis of human adipose tissue-derived mesenchymal stem cells. Cell Prolif. 2008;41:859-874 pubmed publisher
    ..Expressional levels of adipogenic markers regulated by the small interfering RNA of Dkk1 (siDkk1) and sFRP4 (sisFRP4) were assessed using real-time quantitative PCR and Western blot analysis...
  11. Kim K, Park K, Chun E, Choi S, Cho Y, Youn T, et al. A novel biomarker of coronary atherosclerosis: serum DKK1 concentration correlates with coronary artery calcification and atherosclerotic plaques. J Korean Med Sci. 2011;26:1178-84 pubmed publisher
    b>DKK1 modulates Wnt signaling, which is involved in the atherosclerosis. However, no data exist regarding the usefulness of measuring serum DKK1 concentration in predicting coronary atherosclerosis. A total of 270 consecutive patients (62...
  12. Wang S, Liu Y, Ye H, Guo J, Li R, Liu X, et al. Circulating Dickkopf-1 is correlated with bone erosion and inflammation in rheumatoid arthritis. J Rheumatol. 2011;38:821-7 pubmed publisher
    ..01). DKK-1, as an important mediator, was correlated with bone erosion and inflammation in RA. The change of DKK-1 level may serve as a biomarker of disease activity and bone erosion. ..
  13. Wang S, Zhang S. Dickkopf-1 is frequently overexpressed in ovarian serous carcinoma and involved in tumor invasion. Clin Exp Metastasis. 2011;28:581-91 pubmed publisher
    Dickkopf-1 (DKK1) was known as a negative regulator of the Wnt signaling pathway, which played a crucial role in carcinogenesis. However, its function in human cancers remained elusive...
  14. Hall C, Daignault S, Shah R, Pienta K, Keller E. Dickkopf-1 expression increases early in prostate cancer development and decreases during progression from primary tumor to metastasis. Prostate. 2008;68:1396-404 pubmed publisher
    ..The decline of DKK-1 in bone metastases can unmask Wnts' osteoblastic activity. These data support a model in which DKK-1 is a molecular switch that transitions the phenotype of PCa osseous lesions from osteolytic to osteoblastic. ..
  15. Hirata H, Hinoda Y, Nakajima K, Kawamoto K, Kikuno N, Ueno K, et al. Wnt antagonist DKK1 acts as a tumor suppressor gene that induces apoptosis and inhibits proliferation in human renal cell carcinoma. Int J Cancer. 2011;128:1793-803 pubmed publisher
    The functional significance of Wnt antagonist DKK1 has not been investigated in renal cell carcinoma (RCC)...
  16. Ogoshi K, Kasamatsu A, Iyoda M, Sakuma K, Yamatoji M, Sakamoto Y, et al. Dickkopf-1 in human oral cancer. Int J Oncol. 2011;39:329-36 pubmed publisher
    Dickkopf-1 (Dkk1), a negative regulator of the Wnt signaling pathway, is implicated in tumorigenesis in several types of cancer. The purpose of this study was to determine the involvement of Dkk1 in oral squamous cell carcinoma (OSCC)...
  17. Li Z, Yang J, Vazquez E, Rose D, Vakar Lopez F, Mathew P, et al. Low-density lipoprotein receptor-related protein 5 (LRP5) mediates the prostate cancer-induced formation of new bone. Oncogene. 2008;27:596-603 pubmed
    ..PC-3 cells expressed 50 times more Dickkopf-1 (DKK1), an inhibitor of Wnt pathways, than did MDA PCa 2b cells...
  18. Niida A, Hiroko T, Kasai M, Furukawa Y, Nakamura Y, Suzuki Y, et al. DKK1, a negative regulator of Wnt signaling, is a target of the beta-catenin/TCF pathway. Oncogene. 2004;23:8520-6 pubmed
    ..Through computational screening and subsequent experimental analysis, we identified a novel TCF target gene, DKK1, which has been shown to be a potent inhibitor of Wnt signaling...
  19. Qiang Y, Barlogie B, Rudikoff S, Shaughnessy J. Dkk1-induced inhibition of Wnt signaling in osteoblast differentiation is an underlying mechanism of bone loss in multiple myeloma. Bone. 2008;42:669-80 pubmed publisher
    Expression of the Wnt signaling inhibitor, DKK1 by multiple myeloma cells is correlated with lytic bone disease in multiple myeloma. However, the mechanism(s) by which DKK1 contributes to this process is not clear...
  20. Zhou X, Qin X, Zhang X, Ye L. Downregulation of Dickkopf-1 is responsible for high proliferation of breast cancer cells via losing control of Wnt/beta-catenin signaling. Acta Pharmacol Sin. 2010;31:202-10 pubmed publisher
    ..Our finding provides a new insight into the mechanism of breast cancer cell proliferation. ..
  21. Caricasole A, Copani A, Caraci F, Aronica E, Rozemuller A, Caruso A, et al. Induction of Dickkopf-1, a negative modulator of the Wnt pathway, is associated with neuronal degeneration in Alzheimer's brain. J Neurosci. 2004;24:6021-7 pubmed
    ..of the cultures to beta-amyloid peptide (betaAP) induced the expression of the secreted glycoprotein Dickkopf-1 (DKK1)...
  22. Smadja D, d Audigier C, Weiswald L, Badoual C, Dangles Marie V, Mauge L, et al. The Wnt antagonist Dickkopf-1 increases endothelial progenitor cell angiogenic potential. Arterioscler Thromb Vasc Biol. 2010;30:2544-52 pubmed publisher
    ..To determine the role of Wnt antagonist Dickkopf (DKK) 1 in human endothelial colony-forming cells (ECFCs) in view of the emerging importance of Wnt pathways in vascular biology...
  23. Krupnik V, Sharp J, Jiang C, Robison K, Chickering T, Amaravadi L, et al. Functional and structural diversity of the human Dickkopf gene family. Gene. 1999;238:301-13 pubmed
    ..Thus, hDkks 1 and 4 may inhibit Wnt activity by a mechanism upstream of Frizzled. Our findings highlight the structural and functional heterogeneity of human Dkk-related proteins. ..
  24. Heath D, Chantry A, Buckle C, Coulton L, Shaughnessy J, Evans H, et al. Inhibiting Dickkopf-1 (Dkk1) removes suppression of bone formation and prevents the development of osteolytic bone disease in multiple myeloma. J Bone Miner Res. 2009;24:425-36 pubmed publisher
    ..Dickkopf-1 (Dkk1), a soluble inhibitor of wingless/int (Wnt) signaling and osteoblastogenesis, is elevated in patients with MM and ..
  25. 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. ..
  26. Kocemba K, Groen R, van Andel H, Kersten M, Mahtouk K, Spaargaren M, et al. Transcriptional silencing of the Wnt-antagonist DKK1 by promoter methylation is associated with enhanced Wnt signaling in advanced multiple myeloma. PLoS ONE. 2012;7:e30359 pubmed publisher
    ..Wnt signaling promotes proliferation and dissemination, while overexpression of the Wnt inhibitor Dickkopf1 (DKK1) by MM cells contributes to osteolytic bone disease by inhibiting osteoblast differentiation...
  27. Giuliani N, Morandi F, Tagliaferri S, Lazzaretti M, Donofrio G, Bonomini S, et al. Production of Wnt inhibitors by myeloma cells: potential effects on canonical Wnt pathway in the bone microenvironment. Cancer Res. 2007;67:7665-74 pubmed
  28. Navarro D, Agra N, Pestaña A, Alonso J, González Sancho J. The EWS/FLI1 oncogenic protein inhibits expression of the Wnt inhibitor DICKKOPF-1 gene and antagonizes beta-catenin/TCF-mediated transcription. Carcinogenesis. 2010;31:394-401 pubmed publisher
    ..Our results show that EWS/FLI1 inhibits both DKK-1 expression as well as beta-catenin/TCF-dependent transcription, which could contribute to progression of tumours of the Ewing family. ..
  29. Vibhakar R, Foltz G, Yoon J, Field L, Lee H, Ryu G, et al. Dickkopf-1 is an epigenetically silenced candidate tumor suppressor gene in medulloblastoma. Neuro Oncol. 2007;9:135-44 pubmed
    ..Dickkopf-1 (DKK1), a Wnt antagonist, was found to be up-regulated on HDAC inhibition...
  30. Yamaguchi Y, Passeron T, Hoashi T, Watabe H, Rouzaud F, Yasumoto K, et al. Dickkopf 1 (DKK1) regulates skin pigmentation and thickness by affecting Wnt/beta-catenin signaling in keratinocytes. FASEB J. 2008;22:1009-20 pubmed
    ..We previously reported that dickkopf 1 (DKK1) secreted by fibroblasts in the dermis elicits the hypopigmented phenotype of palmoplantar skin due to suppression ..
  31. Bourhis E, Wang W, Tam C, Hwang J, Zhang Y, Spittler D, et al. Wnt antagonists bind through a short peptide to the first ?-propeller domain of LRP5/6. Structure. 2011;19:1433-42 pubmed publisher
    The Wnt pathway inhibitors DKK1 and sclerostin (SOST) are important therapeutic targets in diseases involving bone loss or damage...
  32. Aguilera O, Peña C, Garcia J, Larriba M, Ordóñez Morán P, Navarro D, et al. The Wnt antagonist DICKKOPF-1 gene is induced by 1alpha,25-dihydroxyvitamin D3 associated to the differentiation of human colon cancer cells. Carcinogenesis. 2007;28:1877-84 pubmed
    ..DKK-1 gene induction constitutes a novel mechanism of inhibition of Wnt signalling and antitumour action by 1,25(OH)2D3. ..
  33. Garnero P, Tabassi N, Voorzanger Rousselot N. Circulating dickkopf-1 and radiological progression in patients with early rheumatoid arthritis treated with etanercept. J Rheumatol. 2008;35:2313-5 pubmed
    ..Dkk-1 may be an important mediator of bone erosion in patients with RA. ..
  34. Brott B, Sokol S. Regulation of Wnt/LRP signaling by distinct domains of Dickkopf proteins. Mol Cell Biol. 2002;22:6100-10 pubmed
    ..We report that the effects of Dkks depend on molecular context. Although Wnt8 signaling is inhibited by both Dkk1 and Dkk2 in Xenopus embryos, the same pathway is activated upon interaction of Dkk2 with the Wnt coreceptor LRP6...
  35. Chamorro M, Schwartz D, Vonica A, Brivanlou A, Cho K, Varmus H. FGF-20 and DKK1 are transcriptional targets of beta-catenin and FGF-20 is implicated in cancer and development. EMBO J. 2005;24:73-84 pubmed
    ..Two genes strongly induced in both systems-FGF20 and DKK1-were studied in detail...
  36. Qi L, Sun B, Liu Z, Li H, Gao J, Leng X. Dickkopf-1 inhibits epithelial-mesenchymal transition of colon cancer cells and contributes to colon cancer suppression. Cancer Sci. 2012;103:828-35 pubmed publisher
    This study aimed to determine the expression pattern of dickkopf-1 (Dkk1), a potent inhibitor of Wnt signaling, in colon cancer and to assess the function and mechanism of Dkk1 in tumor progression in vitro and in vivo...
  37. Roessler E, Du Y, Glinka A, Dutra A, Niehrs C, Muenke M. The genomic structure, chromosome location, and analysis of the human DKK1 head inducer gene as a candidate for holoprosencephaly. Cytogenet Cell Genet. 2000;89:220-4 pubmed
    ..We determined the genomic structure of the human gene DKK1 and mapped it to chromosome 10q11.2...
  38. Koppen A, Ait Aissa R, Hopman S, Koster J, Haneveld F, Versteeg R, et al. Dickkopf-1 is down-regulated by MYCN and inhibits neuroblastoma cell proliferation. Cancer Lett. 2007;256:218-28 pubmed
    ..In this study, we show that MYCN suppresses the expression of Dickkopf-1 (DKK1) in both cell lines...
  39. Semenov M, Zhang X, He X. DKK1 antagonizes Wnt signaling without promotion of LRP6 internalization and degradation. J Biol Chem. 2008;283:21427-32 pubmed publisher
    b>DKK1 is a secreted protein that antagonizes Wnt signaling and plays essential roles in vertebrate embryogenesis including head induction, skeletal development, and limb patterning...
  40. Cheng Z, Biechele T, Wei Z, Morrone S, Moon R, Wang L, et al. Crystal structures of the extracellular domain of LRP6 and its complex with DKK1. Nat Struct Mol Biol. 2011;18:1204-10 pubmed publisher
    ..Dickkopf 1 (DKK1) inhibits Wnt signaling by interacting with the extracellular domains of LRP5/6 and is a drug target for multiple ..
  41. Osada H, Tomida S, Yatabe Y, Tatematsu Y, Takeuchi T, Murakami H, et al. Roles of achaete-scute homologue 1 in DKK1 and E-cadherin repression and neuroendocrine differentiation in lung cancer. Cancer Res. 2008;68:1647-55 pubmed publisher
    ..This protein was found to inactivate DKK1 and DKK3, negative regulators of Wnt/beta-catenin signaling, E-cadherin, and integrin beta1 through ASH1-mediated ..
  42. Mao B, Wu W, Davidson G, Marhold J, Li M, Mechler B, et al. Kremen proteins are Dickkopf receptors that regulate Wnt/beta-catenin signalling. Nature. 2002;417:664-7 pubmed
    ..Wnt/beta-catenin signalling is inhibited by the secreted protein Dickkopf1 (Dkk1), a member of a multigene family, which induces head formation in amphibian embryos...
  43. Seifert Held T, Pekar T, Gattringer T, Simmet N, Scharnagl H, Stojakovic T, et al. Circulating Dickkopf-1 in acute ischemic stroke and clinically stable cerebrovascular disease. Atherosclerosis. 2011;218:233-7 pubmed publisher
    ..Our study provides for the first time evidence for a release of Dkk-1 into the circulation in patients with acute ischemic stroke and also in patients with clinically stable cerebrovascular disease. ..
  44. Kuphal S, Lodermeyer S, Bataille F, Schuierer M, Hoang B, Bosserhoff A. Expression of Dickkopf genes is strongly reduced in malignant melanoma. Oncogene. 2006;25:5027-36 pubmed
    ..Our studies thus indicate that loss of DKK-3 expression may contribute to melanoma progression. ..
  45. Wang K, Zhang Y, Li X, Chen L, Wang H, Wu J, et al. Characterization of the Kremen-binding site on Dkk1 and elucidation of the role of Kremen in Dkk-mediated Wnt antagonism. J Biol Chem. 2008;283:23371-5 pubmed publisher
    ..range of developmental, physiological, and pathophysiological processes and is negatively regulated by Dickkopf1 (Dkk1)...
  46. Lee A, He B, You L, Xu Z, Mazieres J, Reguart N, et al. Dickkopf-1 antagonizes Wnt signaling independent of beta-catenin in human mesothelioma. Biochem Biophys Res Commun. 2004;323:1246-50 pubmed
    ..Together, our data suggest that Dkk-1 may be able to antagonize Wnt signaling and exert its tumor suppressive effects through beta-catenin-independent non-canonical pathways (i.e., the Wnt/JNK pathway). ..
  47. Tung E, Mak C, Fatima S, Lo R, Zhao H, Zhang C, et al. Clinicopathological and prognostic significance of serum and tissue Dickkopf-1 levels in human hepatocellular carcinoma. Liver Int. 2011;31:1494-504 pubmed publisher
    Although Dickkopf-1 (DKK1) is known to be a negative regulator of the Wnt/?-catenin pathway, it has been recently found to be upregulated in cancers...
  48. Gunn W, Conley A, Deininger L, Olson S, Prockop D, Gregory C. A crosstalk between myeloma cells and marrow stromal cells stimulates production of DKK1 and interleukin-6: a potential role in the development of lytic bone disease and tumor progression in multiple myeloma. Stem Cells. 2006;24:986-91 pubmed
    ..were higher in undifferentiated MSCs than in MSCs treated with osteogenic medium, remained high in the presence of Dkk1, and were reduced by BIO treatment...
  49. Yu B, Yang X, Xu Y, Yao G, Shu H, Lin B, et al. Elevated expression of DKK1 is associated with cytoplasmic/nuclear beta-catenin accumulation and poor prognosis in hepatocellular carcinomas. J Hepatol. 2009;50:948-57 pubmed publisher
    To assess the value of Dickkopf-1 (DKK1) for predicting clinical outcome of human hepatocellular carcinoma (HCC) in patients with HCC...
  50. Leijten J, Emons J, Sticht C, Van Gool S, Decker E, Uitterlinden A, et al. Gremlin 1, frizzled-related protein, and Dkk-1 are key regulators of human articular cartilage homeostasis. Arthritis Rheum. 2012;64:3302-12 pubmed publisher
    ..As hypertrophic differentiation of articular cartilage may contribute to the development of OA, our findings may open new avenues for therapeutic intervention. ..
  51. Peng S, Miao C, Li J, Fan X, Cao Y, Duan E. Dickkopf-1 induced apoptosis in human placental choriocarcinoma is independent of canonical Wnt signaling. Biochem Biophys Res Commun. 2006;350:641-7 pubmed
    ..Together, our data indicate the possible correlation between Dkk-1 and human placental choriocarcinoma and suggest potential applications of Dkk-1 in treatment of human placental choriocarcinomas. ..
  52. Pfaff E, Becker S, Gunther A, Konigshoff M. Dickkopf proteins influence lung epithelial cell proliferation in idiopathic pulmonary fibrosis. Eur Respir J. 2011;37:79-87 pubmed publisher
    ..Enhanced expression of DKK1 and DKK4 and KRM1 was detected in lung homogenates of IPF patients compared with transplant donors...
  53. Thudi N, Martin C, Murahari S, Shu S, Lanigan L, Werbeck J, et al. Dickkopf-1 (DKK-1) stimulated prostate cancer growth and metastasis and inhibited bone formation in osteoblastic bone metastases. Prostate. 2011;71:615-25 pubmed publisher
    ..The present study showed that DKK-1 is a potent inhibitor of bone growth in prostate cancer-induced osteoblastic metastases. ..
  54. Ke H, Richards W, Li X, Ominsky M. Sclerostin and Dickkopf-1 as therapeutic targets in bone diseases. Endocr Rev. 2012;33:747-83 pubmed publisher
    ..role in bone formation and regeneration, and expression of two Wnt pathway inhibitors, sclerostin and Dickkopf-1 (DKK1), appears to be associated with changes in bone mass...
  55. Christodoulides C, Laudes M, Cawthorn W, Schinner S, Soos M, O Rahilly S, et al. The Wnt antagonist Dickkopf-1 and its receptors are coordinately regulated during early human adipogenesis. J Cell Sci. 2006;119:2613-2620 pubmed publisher
    ..We present the first evidence that a Wnt antagonist, Dickkopf 1 (Dkk1), is secreted by human preadipocytes and promotes adipogenesis...
  56. Qiao L, Xu Z, Zhao T, Ye L, Zhang X. Dkk-1 secreted by mesenchymal stem cells inhibits growth of breast cancer cells via depression of Wnt signalling. Cancer Lett. 2008;269:67-77 pubmed publisher
    ..Overexpression of Dkk-1 in Z3 cells enhanced the inhibition. Therefore, Dkk-1 secreted by Z3 cells involves the inhibition via the Wnt pathway. ..
  57. Dong L, Qu L, Chu L, Zhang X, Liu Y. Serum level of DKK-1 and its prognostic potential in non-small cell lung cancer. Diagn Pathol. 2014;9:52 pubmed publisher
    ..The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1471414150119415. ..
  58. Yi N, Liao Q, Li T, Xiong Y. Novel expression profiles and invasiveness-related biology function of DKK1 in endometrial carcinoma. Oncol Rep. 2009;21:1421-7 pubmed
    b>DKK1 is a negative regulator in the Wnt signal transduction pathway. It can inhibit the pathway's activation...
  59. Korvala J, Löija M, Makitie O, Sochett E, Juppner H, Schnabel D, et al. Rare variations in WNT3A and DKK1 may predispose carriers to primary osteoporosis. Eur J Med Genet. 2012;55:515-9 pubmed publisher
    ..The genes studied included DKK1, DKK2, WNT3A, WNT10B, AXIN1, SOST, TPH1 and 5-HTR1B. Two rare variants in WNT3A (c.152A > G, p...
  60. Yamaguchi Y, Itami S, Watabe H, Yasumoto K, Abdel Malek Z, Kubo T, et al. Mesenchymal-epithelial interactions in the skin: increased expression of dickkopf1 by palmoplantar fibroblasts inhibits melanocyte growth and differentiation. J Cell Biol. 2004;165:275-85 pubmed
    ..Using cDNA microarray analysis, fibroblasts derived from palmoplantar skin expressed high levels of dickkopf 1 (DKK1; an inhibitor of the canonical Wnt signaling pathway), whereas nonpalmoplantar fibroblasts expressed higher levels ..
  61. Voorzanger Rousselot N, Goehrig D, Journe F, Doriath V, Body J, Clezardin P, et al. Increased Dickkopf-1 expression in breast cancer bone metastases. Br J Cancer. 2007;97:964-70 pubmed
    ..Measurements of circulating Dkk-1 levels may be useful for the clinical investigation of patients with breast cancer and bone metastases. ..
  62. Feldmann R, Schierl M, Fink A, Sator P, Maiweg J, Steiner A. Serum levels of glycoprotein Dickkopf-1 in patients with cutaneous malignant melanoma: a prospective pilot study. Dermatology. 2011;222:171-5 pubmed publisher
    ..It was shown previously that Dkk-1 activates cell death in melanoma cells. Our in vivo data indicate that a decrease in Dkk-1 could be a sign of loss of tumor control. ..
  63. Xu W, Liu Z, Yang C, Qin W, Shao Z. Expression of dickkopf-1 and beta-catenin related to the prognosis of breast cancer patients with triple negative phenotype. PLoS ONE. 2012;7:e37624 pubmed publisher
    We investigated the prognostic importance of dickkopf-1(DKK1) and beta-catenin expression in triple negative breast cancers. The expression of DKK1 and beta-catenin was evaluated in breast cell lines using RT-PCR and western blot...
  64. Wang X, Wang K, Han L, Zhang A, Shi Z, Zhang K, et al. PRDM1 is directly targeted by miR-30a-5p and modulates the Wnt/?-catenin pathway in a Dkk1-dependent manner during glioma growth. Cancer Lett. 2013;331:211-9 pubmed publisher
    ..malignancy by negatively modulating Wnt/?-catenin signaling and this modulation was dependent on the Wnt inhibitor Dkk1. Using bioinformatics and biological approaches, we found that PRDM1 was a direct target of miR-30a-5p, and PRDM1 ..
  65. Krause U, Ryan D, Clough B, Gregory C. An unexpected role for a Wnt-inhibitor: Dickkopf-1 triggers a novel cancer survival mechanism through modulation of aldehyde-dehydrogenase-1 activity. Cell Death Dis. 2014;5:e1093 pubmed publisher
    ..This is the first report linking Dkk-1 to tumor stress resistance, further supporting the targeting of Dkk-1 not only to prevent and treat osteolytic bone lesions but also to reduce numbers of stress-resistant tumor cells. ..
  66. Shen Q, Fan J, Yang X, Tan Y, Zhao W, Xu Y, et al. Serum DKK1 as a protein biomarker for the diagnosis of hepatocellular carcinoma: a large-scale, multicentre study. Lancet Oncol. 2012;13:817-26 pubmed publisher
    ..We assessed whether measurement of Dickkopf-1 (DKK1) in serum could improve diagnostic accuracy for HCC...
  67. Tao Y, Liu Z, Liu H. Dickkopf-1 (DKK1) promotes invasion and metastasis of hepatocellular carcinoma. Dig Liver Dis. 2013;45:251-7 pubmed publisher
    Dickkopf-1 (DKK1) recently has been reported to be involved in the progress of hepatocellular carcinoma, but its concrete role is not clear...
  68. Li Y, Chen J, Lu W, McCormick L, Wang J, Bu G. Mesd binds to mature LDL-receptor-related protein-6 and antagonizes ligand binding. J Cell Sci. 2005;118:5305-14 pubmed
    ..Together our results show that in addition to serving as a folding chaperone, Mesd can function as a receptor antagonist by inhibiting ligand binding to mature LRP6. ..
  69. David R, Brenner C, Stieber J, Schwarz F, Brunner S, Vollmer M, et al. MesP1 drives vertebrate cardiovascular differentiation through Dkk-1-mediated blockade of Wnt-signalling. Nat Cell Biol. 2008;10:338-45 pubmed publisher
    ..This may also provide a tool to elicit cardiac transdifferentiation in native human adult stem cells. ..
  70. Goliasch G, Wiesbauer F, Kastl S, Katsaros K, Blessberger H, Maurer G, et al. Premature myocardial infarction is associated with low serum levels of Wnt-1. Atherosclerosis. 2012;222:251-6 pubmed publisher
    ..Wnt-1 is associated with markers of glucose and lipid metabolism. Further research elucidating the role of Wnt pathways in premature coronary artery disease and metabolic syndrome is warranted. ..
  71. Ai M, Holmen S, Van Hul W, Williams B, Warman M. Reduced affinity to and inhibition by DKK1 form a common mechanism by which high bone mass-associated missense mutations in LRP5 affect canonical Wnt signaling. Mol Cell Biol. 2005;25:4946-55 pubmed
    ..All HBM mutant proteins had reduced physical interaction with and reduced inhibition by DKK1. These data suggest that HBM mutant proteins can transit to the cell surface in sufficient quantity to transduce ..
  72. Holm H, Gudbjartsson D, Arnar D, Thorleifsson G, Thorgeirsson G, Stefansdottir H, et al. Several common variants modulate heart rate, PR interval and QRS duration. Nat Genet. 2010;42:117-22 pubmed publisher
    ..00032, respectively), between TBX5 and advanced atrioventricular block (P = 0.0067), and between SCN10A and pacemaker implantation (P = 0.0029). We also replicated previously described associations with the QT interval. ..
  73. Rawson J, Manno M, Mrkonjic M, Daftary D, Dicks E, Buchanan D, et al. Promoter methylation of Wnt antagonists DKK1 and SFRP1 is associated with opposing tumor subtypes in two large populations of colorectal cancer patients. Carcinogenesis. 2011;32:741-7 pubmed publisher
    Aberrant activation of canonical Wnt signaling is a hallmark event in colorectal carcinogenesis. The Dickkopf-1 (DKK1) and Secreted Frizzled Related Protein 1 (SFRP1) genes encode extracellular inhibitors of Wnt signaling that are ..
  74. Piters E, Balemans W, Nielsen T, Andersen M, Boudin E, Brixen K, et al. Common genetic variation in the DKK1 gene is associated with hip axis length but not with bone mineral density and bone turnover markers in young adult men: results from the Odense Androgen Study. Calcif Tissue Int. 2010;86:271-81 pubmed publisher
    ..Our objective was to evaluate the effect of DKK1 polymorphisms on bone mineral density (BMD), hip geometry, and bone turnover...
  75. Glantschnig H, Hampton R, Lu P, Zhao J, Vitelli S, Huang L, et al. Generation and selection of novel fully human monoclonal antibodies that neutralize Dickkopf-1 (DKK1) inhibitory function in vitro and increase bone mass in vivo. J Biol Chem. 2010;285:40135-47 pubmed publisher
    ..signaling is a central regulatory component of bone formative and resorptive activities, and the pathway inhibitor DKK1 is a suppressor of bone formation and bone mass accrual in mice...
  76. Zorn A. Wnt signalling: antagonistic Dickkopfs. Curr Biol. 2001;11:R592-5 pubmed
    ..Dickkopf1 binds to the LRP5/6 Wnt co-receptor and prevents the formation of active Wnt--Frizzled--LRP5/6 receptor complexes, thus blocking the canonical Wnt--beta-catenin pathway. ..
  77. Sikandar S, Dizon D, Shen X, Li Z, Besterman J, Lipkin S. The class I HDAC inhibitor MGCD0103 induces cell cycle arrest and apoptosis in colon cancer initiating cells by upregulating Dickkopf-1 and non-canonical Wnt signaling. Oncotarget. 2010;1:596-605 pubmed
    ..Our studies also provide novel insights into roles for DKK1 in addition to canonical WNT signaling and the mechanism of CCIC tumor formation.
  78. Bafico A, Liu G, Goldin L, Harris V, Aaronson S. An autocrine mechanism for constitutive Wnt pathway activation in human cancer cells. Cancer Cell. 2004;6:497-506 pubmed
    ..Extracellular Wnt antagonists FRP1 and DKK1 caused a dramatic downregulation of beta-catenin levels in these tumor cells associated with alteration of ..
  79. de Rooy D, Yeremenko N, Wilson A, Knevel R, Lindqvist E, Saxne T, et al. Genetic studies on components of the Wnt signalling pathway and the severity of joint destruction in rheumatoid arthritis. Ann Rheum Dis. 2013;72:769-75 pubmed publisher
    ..Dickkopf-1 (Dkk-1) and sclerostin (Sost) are negative regulators and lipoprotein receptor-related protein-5 (LRP-5) and Kremen-1 are transmembrane receptors involved in this pathway...
  80. Takahashi N, Fukushima T, Yorita K, Tanaka H, Chijiiwa K, Kataoka H. Dickkopf-1 is overexpressed in human pancreatic ductal adenocarcinoma cells and is involved in invasive growth. Int J Cancer. 2010;126:1611-20 pubmed publisher
  81. Moors M, Bose R, Johansson Haque K, Edoff K, Okret S, Ceccatelli S. Dickkopf 1 mediates glucocorticoid-induced changes in human neural progenitor cell proliferation and differentiation. Toxicol Sci. 2012;125:488-95 pubmed publisher
    ..Analysis of pathway-specific genes revealed that Dex induces an upregulation of the Wnt-signaling antagonist DKK1. Moreover, Dex- or DKK1-treated hNPCs showed reduced transcriptional levels of the two canonical Wnt target genes ..
  82. Tian E, Zhan F, Walker R, Rasmussen E, Ma Y, Barlogie B, et al. The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma. N Engl J Med. 2003;349:2483-94 pubmed
    ..One of these genes, dickkopf 1 (DKK1), and its corresponding protein (DKK1) were studied in detail because DKK1 is a secreted factor that has been ..
  83. Ko J, Wang F, Wang C, Wong T, Chou W, Tseng S. Increased Dickkopf-1 expression accelerates bone cell apoptosis in femoral head osteonecrosis. Bone. 2010;46:584-91 pubmed publisher
    Intensive bone cell apoptosis contributes to osteonecrosis of femoral head (ONFH). Dickkopf-1 (DKK1) reportedly mediates various types of skeletal disorders. This study investigated whether DKK1 was linked to the occurrence of ONFH...
  84. Diarra D, Stolina M, Polzer K, Zwerina J, Ominsky M, Dwyer D, et al. Dickkopf-1 is a master regulator of joint remodeling. Nat Med. 2007;13:156-63 pubmed
    ..We identified tumor necrosis factor-alpha (TNF) as a key inducer of DKK-1 in the mouse inflammatory arthritis model and in human rheumatoid arthritis. These results suggest that the Wnt pathway is a key regulator of joint remodeling. ..
  85. Liu Y, Kodithuwakku S, Ng P, Chai J, Ng E, Yeung W, et al. Excessive ovarian stimulation up-regulates the Wnt-signaling molecule DKK1 in human endometrium and may affect implantation: an in vitro co-culture study. Hum Reprod. 2010;25:479-90 pubmed publisher
    ..Expression of several Wnt-signaling transcripts, including Dickkopf homolog 1 (DKK1), DKK2 and secreted frizzled-related protein 4 (sFRP4), was analyzed throughout the menstrual cycle...
  86. Mikheev A, Mikheeva S, Maxwell J, Rivo J, Rostomily R, Swisshelm K, et al. Dickkopf-1 mediated tumor suppression in human breast carcinoma cells. Breast Cancer Res Treat. 2008;112:263-73 pubmed
    ..Thus, our study supports the hypothesis that DKK-1 mediated tumor suppressor effect is independent of beta-catenin dependent transcription and identified the CamKII pathway that contributes into DKK-1 signaling. ..
  87. Darlavoix T, Seelentag W, Yan P, Bachmann A, Bosman F. Altered expression of CD44 and DKK1 in the progression of Barrett's esophagus to esophageal adenocarcinoma. Virchows Arch. 2009;454:629-37 pubmed publisher
    ..Marker expression was studied by immunohistochemistry using antibodies against CD44, DKK1, CDX2, COX2, SOX9, OCT1, E-cadherin, and beta-catenin. Immunostaining was evaluated semi-quantitatively...
  88. Politou M, Heath D, Rahemtulla A, Szydlo R, Anagnostopoulos A, Dimopoulos M, et al. Serum concentrations of Dickkopf-1 protein are increased in patients with multiple myeloma and reduced after autologous stem cell transplantation. Int J Cancer. 2006;119:1728-31 pubmed
    ..These results could provide the basis for developing agents that block DKK-1, thus restoring osteoblast function and counteracting the increased osteoclastogenesis observed in myeloma. ..
  89. Balemans W, Piters E, Cleiren E, Ai M, Van Wesenbeeck L, Warman M, et al. The binding between sclerostin and LRP5 is altered by DKK1 and by high-bone mass LRP5 mutations. Calcif Tissue Int. 2008;82:445-53 pubmed publisher
    ..In the present study, we investigated six different HBM-LRP5 mutations and confirm that neither Dickkopf1 (DKK1) nor sclerostin efficiently inhibits HBM-LRP5 signaling...
  90. Filipovich A, Gandhirajan R, Gehrke I, Poll Wolbeck S, Kreuzer K. Evidence for non-functional Dickkopf-1 (DKK-1) signaling in chronic lymphocytic leukemia (CLL). Eur J Haematol. 2010;85:309-13 pubmed publisher
    ..It is thought to be responsible for the extended survival of CLL cells in vivo. Dickkopf1 (DKK1) is known to antagonize Wnt signaling by direct high-affinity binding to the extracellular domain of WNT coreceptor ..
  91. Purro S, Dickins E, Salinas P. The secreted Wnt antagonist Dickkopf-1 is required for amyloid ?-mediated synaptic loss. J Neurosci. 2012;32:3492-8 pubmed publisher
    ..The expression of the Wnt antagonist Dickkopf-1 (Dkk1) is increased in brains of AD patients and in AD transgenic mouse models, suggesting that dysfunction of Wnt ..
  92. Killick R, Ribe E, Al Shawi R, Malik B, Hooper C, Fernandes C, et al. Clusterin regulates ?-amyloid toxicity via Dickkopf-1-driven induction of the wnt-PCP-JNK pathway. Mol Psychiatry. 2014;19:88-98 pubmed publisher
    ..remained elusive, it is known to increase the expression of the antagonist of canonical wnt signalling, Dickkopf-1 (Dkk1), whereas the silencing of Dkk1 blocks A? neurotoxicity...