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. Data suggest a critical role of dickkopf 4 (DKK4) in docetaxel resistance of the lung adenocarcinoma A549 (A549/DTX) cells. PMID: 28981599
2. in NOD/SCID mice supplemented with high glucose, HepG2 xenografted tumors grew rapidly in which elevated levels of beta-catenin, c-Myc and decreased levels of DKK4 were detected. Knockdown of DKK4 by shRNA promotes proliferation of HCC cells in NG, which is suppressed by treating cells exogenously with recombinant DKK4 protein. Our in vitro and in vivo results indicate an important functional role of DKK4 in glucose fa... PMID: 27272409
3. Our results indicated that DKK4 might be contributed to predicting EOC progression and prognosis. DKK4 could promote the invasion of EOC through JNK activation. PMID: 28666421
4. We found that TCF7L1 recruits the C-terminal binding protein (CtBP) and histone deacetylase 1 (HDAC1) to the DKK4 promoter to repress DKK4 gene expression. In the absence of TCF7L1, TCF7L2 and beta-catenin occupancy at the DKK4 promoter is stimulated and DKK4 expression is increased. These findings uncover a critical role for TCF7L1 in repressing DKK4 gene expression to promote the oncogenic potential of CRCs. PMID: 28450117
5. DKK4 expression is significantly upregulated in human masticatory mucosa during wound healing PMID: 28005267
6. DKK4 may have function on the development and progression of pancreatic cancer. PMID: 26880586
7. The recurrence of benign tumors of mammary gland occurred predominantly in women-carriers of mutant alleles with polymorphism rs8190924 of gene GSR and AA rs3763511of gene DKK4. PMID: 26419038
8. DKK4 upregulated by T3/TR antagonizes the Wnt signal pathway to suppress tumor cell progression PMID: 23958302
9. rs3923086 in AXIN2 and rs3763511 in DKK4 that did not show any association in the overall population were significantly associated with early on-set and estrogen receptor negative breast cancers, respectively. PMID: 23516639
10. It would appear that deregulation of the WNT pathway by overexpression of DKK4 may further impair WNT signaling and lead to Anorectal malformations. PMID: 23108157
11. Our findings suggest a potential tumour suppressive role of DKK4 as well as that of an important regulator of HCC. PMID: 22249261
12. Found the unique expression of the Wnt antagonist DKK4 in SW480APC, but not parental SW480 cell-derived exosomes. Upregulation of DKK4 in SW480APC cells was confirmed by RT-PCR, immunoblotting, and immunogold electron microscopy. PMID: 22740476
13. The TR/DKK4/Wnt/beta-catenin cascade influences the proliferation and migration of hepatoma cells during the metastasis process and support a tumor suppressor role of the thyroid hormone receptor. PMID: 21994129
14. TFAP2E hypermethylation is associated with clinical nonresponsiveness to chemotherapy in colorectal cancer. Functional assays confirm that TFAP2E-dependent resistance is mediated through DKK4. PMID: 22216841
15. Polymorphism of DKK4 was significantly associated with brain volume in Chinese individuals. PMID: 21341386
16. chromosome 8 mapping by FISH PMID: 11701963
17. DKK4 may play a role in schizophrenia pathogenesis PMID: 17553464
18. DICKKOPF-4 is induced by TCF/beta-catenin and upregulated in human colon cancer, promotes tumour cell invasion and angiogenesis. PMID: 18408752
19. DKK4 is an important negative regulator of colon cancer cell growth. PMID: 19059704
20. Dickkopf-4 and -2 are significantly upregulated in most colorectal tumors PMID: 19659606

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Secreted.

Dickkopf family

Expressed in cerebellum, T-cells, esophagus and lung.

HGNC: 2894

OMIM: 605417

KEGG: hsa:27121

STRING: 9606.ENSP00000220812

UniGene: Hs.159311