Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt and by forming a ternary complex with the transmembrane protein KREMEN that promotes internalization of LRP5/6. DKKs play an important role in vertebrate development, where they locally inhibit Wnt regulated processes such as antero-posterior axial patterning, limb development, somitogenesis and eye formation. In the adult, Dkks are implicated in bone formation and bone disease, cancer and Alzheimer disease.

1. our findings demonstrate that DKK2 functions as a tumor suppressor through inhibiting cell proliferation and inducing apoptosis via regulating Wnt signaling during breast tumorigenesis. PMID: 28467796
2. Knock down of the dickkopf WNT signaling pathway inhibitor 2 (DKK2) resulted in a significant suppression of HOXD10, HOXD11 and HOXD13 while over-expression of DKK2 and stimulation with factors of the WNT signaling pathway. PMID: 27363011
3. epigenetic silencing of Wnt antagonists was associated with gastric carcinogenesis, and concurrent hypermethylation of SFRP2 and DKK2 could be a potential marker for a prognosis of poor overall survival. PMID: 28152305
4. the genotyping and functional findings are consistent with the hypothesis that DKK2 is a tumor suppressor; by selectively retaining a transcriptionally inactive DKK2 allele, the reduction of DKK2 function results in unchecked Wnt/beta-catenin signaling, contributing to hepatocellular carcinoma oncogenesis. PMID: 27203079
5. The present report suggested that DKK2 downregulation suppressed the proliferation and invasion of prostate cancer cells by inhibiting the Wnt/betacatenin signaling pathway. PMID: 27431620
6. these findings reveal that the miR-187-5p-DKK2 pathway regulates Wnt/beta-catenin signaling, cell growth, and apoptosis. Our findings provide the first evidence of a role for miR-187-5p in promotion of B-cell ALL. PMID: 27296949
7. Genetic variant in DKK2 gene is associated with gallbladder cancer. PMID: 26715268
8. targeting of DKK2 by miR-154 leads to upregulation of beta-catenin expression and activation of the classical Wnt signaling pathway and cardiac fibroblasts. PMID: 27542661
9. MiR-21 overexpression was significantly correlated with the DKK2-/beta-catenin- immunohistochemical phenotype. PMID: 23999978
10. Data indicate that inhibiting dickkopf-related protein 2 (DKK2)with siDKK2 reduced the expression of DKK2, but had no effect on leptin expression. PMID: 25312721
11. We found 1 DKK2 SNP to be significantly associated with alcohol-related harm in alcoholic subjects PMID: 24117450
12. a new regulatory mechanism of miR-222 PMID: 23587485
13. Our results provide strong evidence that DKK2 is a key player in Ewing sarcoma invasion and osteolysis and also in the differential phenotype of Ewing sarcoma cells. PMID: 23204234
14. DKK2 may contribute to tumorigenesis in epithelial ovarian cancer(EOC) through the Wnt/beta-catenin signaling mechanisms. PMID: 22964660
15. Elevated TGF-beta1 levels in osteoarthritic osteoblasts can stimulate DKK2 expression. PMID: 21312269
16. In the study of the genetics of alcoholism, three SNPs in DKK2 (rs427983; rs419558; rs399087) demonstrated empirical significance. PMID: 20332099
17. DKK2 is epigenetically silenced by methylation in higher grades and stages of renal cell carcinoma; results suggest that DKK2 inhibits renal cancer progression through apoptotic and cell cycle pathways PMID: 19755393
18. Analysis of individual Dkk domains and chimeric Dkks shows that the carboxy-terminal domains of both Dkk1 & 2 associate with LRP6 and are necessary and sufficient for Wnt8 inhibition. PMID: 12167704
19. analysis of the structural basis of the interaction between Dkk and low density lipoprotein receptor-related protein (LRP) 5/6 PMID: 18524778

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Secreted.

Dickkopf family

Expressed in heart, brain, skeletal muscle and lung.

HGNC: 2892

OMIM: 605415

KEGG: hsa:27123

STRING: 9606.ENSP00000285311

UniGene: Hs.211869