DKK1是一種調(diào)節(jié)細(xì)胞分化和增殖的蛋白質(zhì)。最新的研究表明，DKK1在許多疾病中都扮演著重要角色。例如，它與骨質(zhì)疏松、糖尿病、癌癥、風(fēng)濕性關(guān)節(jié)炎等疾病的發(fā)病機(jī)制密切相關(guān)。近期的一些研究還表明，DKK1參與了神經(jīng)系統(tǒng)發(fā)育和退化過(guò)程，與阿爾茨海默病等神經(jīng)系統(tǒng)疾病有關(guān)。此外，DKK1的過(guò)度表達(dá)還被發(fā)現(xiàn)與器官纖維化和損傷修復(fù)等過(guò)程中的組織重塑相關(guān)。因此，DKK1在疾病發(fā)病機(jī)制和治療中具有潛在的應(yīng)用價(jià)值。

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. Inhibits the pro-apoptotic function of KREMEN1 in a Wnt-independent manner, and has anti-apoptotic activity.

1. Results provide evidence that DKK-1 is involved in the progression of prostate cancer (PC). DKK-1-mediated inhibition of osteoblasts, which contributes to tumor progression and osteolytic metastases, may also play a role in the development of metastases with osteoblastic features. PMID: 30116403
2. our findings suggest that glucocorticoid-induced expression of Dkk-1 could be a key factor in modulating the differentiation ability of MSCs used for osteonecrosis of the femur head and other stem cell therapies. PMID: 29084466
3. MicroRNA152 inhibits cell proliferation of osteosarcoma through DKK1. PMID: 29845282
4. this study shows that DKK1 is increased in vitiligo in lesional and peri-lesional skin of acral and non-acral lesions PMID: 29605863
5. Dkk-1 and PTH levels in psoriatic arthritis are lower than healthy female controls, in contrast with rheumatoid arthritis, in which they are increased PMID: 28634697
6. this study suggests that higher expression of DKK1 in the dermis induced senescence in melanocytes that may lead to hypopigmentation and play role in vitiligo pathogenesis PMID: 29442138
7. TNF-alpha, DKK1, and OPG have roles in pathogenesis of knee osteoarthritis PMID: 28676900
8. Serum level of DKK-1 is elevated in patients with rheumatoid arthritis (RA) compared to healthy controls, suggesting an important role of DKK-1 in the pathogenesis and treatment of RA [review]. PMID: 29665496
9. the staining intensity of DKK1 was significantly stronger in the placentas of the severe preeclampsia group PMID: 29603045
10. Serum OPN and DKK1 levels of hepatocellular carcinoma patients could be considered as novel biomarkers showing prognostic significance after hepatectomy based on long-term survival data PMID: 29753515
11. These findings suggested that decreased circulating DKK-1 levels are associated with the development and severity of exudative age-related macular degeneration, and have potential to become a biomarker for exudative age-related macular degeneration. PMID: 28455497
12. In patients with rheumatoid arthritis, higher levels of DKK1 were found in patients with lower functional status.This could be explained by more structural damage; DKK1 could be used as a biomarker of joint destruction in RA. PMID: 29282619
13. The Dickkopf-1 (DKK1) is a secreted inhibitor of beta-catenin-dependent Wnt signalling and was originally characterized as a tumour suppressor based on the prevailing view that Wnt signalling promotes cancer pathogenesis. PMID: 28574171
14. Collectively, our data strongly suggest that stress-related neurohormones, such as GCs, cause DP cells to secrete DKK1, which in turn inhibits hair growth. PMID: 28155238
15. the inhibitory effects of silencing miR-217 on stem cell properties and Wnt signaling were reversed by the downregulation of DKK1 in miR-217-downregulated cells. Therefore, our results indicate that miR-217 plays a vital role in the CSC-like phenotypes of Hepatocellular carcinoma (HCC) cells and may be used as a potential therapeutic target against HCC. PMID: 28849121
16. In our cohort of pregnant women, sclerostin and DKK1 were not associated with any adverse metabolic profile, and possibly do not play relevant roles in the pathophysiology of gestational diabetes mellitus. PMID: 28277306
17. Serum DKK-1 levels in axial spondyloarthritis depend on disease duration. As disease duration increases, DKK-1 serum levels decrease. PMID: 27297260
18. inhibition of the mTOR pathway increases sensitivity of melanoma cells towards temozolomide, which is associated with enhanced expression of the Wnt antagonist DKK1 PMID: 28423208
19. Inhibition of DKK1 expression effectively decrease plaque stability by attenuating endoplasmic reticulum stress-mediated cellular apoptosis through intiating the JNK pathway and inhibiting Wnt/betacatenin and following by activation of the IRE1alpha and eif2alpha/CHOP pathways. PMID: 28703797
20. This study demonstrated that DKK-1 may be a predictor for prognosis in pancreatic ductal adenocarcinoma patients. PMID: 28749252
21. synovial fluid Dkk-1 levels are positively related to the severity of joint damage in knee osteoarthritis. PMID: 28451870
22. DKK1 exerts its pro-invasion function at least in part through the beta-catenin/ MMP-7 signaling pathway, suggesting DKK1 as a potential therapeutic target for human hilar cholangiocarcinoma (HCCA). PMID: 27608843
23. Sclerostin But Not Dickkopf-1 has roles in increasing prevalence of osteoporotic fracture and lower bone mineral density in postmenopausal Korean women PMID: 27289555
24. High serum levels of sclerostin and Dkk-1 are associated with acute ischaemic stroke PMID: 27573735
25. regulated by Dkk-1 secreted by Multiple Myeloma cells and is a potential mechanism contributing to the osteoblast dysfunction noted in Multiple Myeloma. PMID: 26763740
26. DKK1 c.121G>A (p.(A41T)) variant was identified in the family with Chiari malformation type 1. Screening of DKK1 in a cohort of 65 CMI sporadic patients identified another missense variant, the c.359G>T (p.(R120L)), in two unrelated patients. PMID: 28513615
27. LRP6 ectodomain becomes highly compact upon complexation with the Wnt antagonist Dkk1, suggesting a potential role for the ectodomain conformational change in the regulation of receptor oligomerization and signaling. PMID: 28052259
28. Our results suggest that measurement of DKK-1 combined with DKK-1 autoantibodies is a potentially valuable tool for the early detection of ESCC. PMID: 26988995
29. TET1 potently inhibited canonical Wnt/beta-catenin signaling by demethylating and upregulating two upstream antagonists of this pathway, SFRP2 and DKK1, which was associated with inhibition of EMT and cancer cell metastasis. PMID: 28851501
30. This is the first study demonstrating a link between B cell depletion and skin Dkk-1 upregulation in patients with systemic sclerosis PMID: 27208972
31. We found significantly increased levels of DKK-1 in patients with acute CO poisoning, compared to healthy controls. High levels of serum DKK-1 in patients were significantly correlated with severe neurological symptoms. PMID: 27353797
32. DKK1 prevents lung metastasis of breast cancer cells but promotes breast-to-bone metastasis. PMID: 28892080
33. Structure of the dual-mode Wnt regulator Kremen1 and insight into ternary complex formation with LRP6 and DKK1 have been presented. PMID: 27524201
34. Expression of Cancer stem cells-associated DKK1 mRNA might be an unfavorable prognostic marker for patients with hepatocellular carcinoma. PMID: 28870909
35. In chronic kidney disease, serum levels of the Wnt inhibitors DKK1 and sclerostin are unrelated, indicating different sites of origin and/ or different regulatory mechanisms. Sclerostin, as opposed to DKK1, may qualify as a biomarker of chronic kidney disease-mineral and bone and mineral disorder (CKD-MBD), particularly in dialysis patients. PMID: 28493902
36. endogenous expression of the WNT antagonists DKK1 and FRZB is necessary for multiple steps during chondrogenesis PMID: 27733096
37. The expression level of DKK1 in serum was increased in breast cancer patients, suggesting that serum expression level of DKK1 could be a useful biomarker in breast cancer. PMID: 28248066
38. Results show that the expression of DKK1 is elevated in human HBV-related hepatocellular carcinoma tissues. PMID: 28419472
39. DKK-1 and PDCD5 can be independent predictors of overall survival in patients suffering from chondrosarcoma. PMID: 27255549
40. In patients with hepatocellular carcinoma serum DKK1 level correlated with tumor size, consequently, patients with bigger tumors tend to have higher levels of DKK1. PMID: 27161933
41. Our results indicate that DKK1 and SFRP1 may be potentially useful biomarkers for evaluating the beneficial effects of long-term exercise on physical fitness and metabolism as well as the prognosis of patients with cancer. PMID: 28178355
42. Dickkopf-1 and sclerostin were never correlated with each other or with bone turnover markers patients with Paget's disease of bone PMID: 28054306
43. these findings suggest that DKK1 induces the occurrence of epithelial-mesenchymal transition and promotes migration and invasion in non-small cell lung cancer cells. Mechanically, b-catenin plays a vital role in DKK1-induced non-small cell lung cancer cell migration and invasion, and DKK1 inhibits the phosphorylation of b-catenin, resulting in the increased nuclear localization of b-catenin. PMID: 28677426
44. Results suggest that miR-107 is likely to inhibit the occurrence and development of osteosarcoma by down-regulating Dkk-1 via the Wnt/beta-catenin signaling pathway. PMID: 28682874
45. Recombinant Dkk1 suppresses beta-catenin target genes in myeloid-derived suppressor cells (MDSCs) from mice and humans and anti-Dkk1 loses its antitumor effects in mice lacking beta-catenin in myeloid cells or after depletion of MDSCs, demonstrating that Dkk1 directly targets MDSCs. PMID: 27045006
46. Luciferase-fused 3' untranslated region of human Dickkopf1 activity was highly upregulated in A1CF-overexpressed MCF7 cells, but this upregulation can be inhibited by mutating conserved binding motifs of Dickkopf1 3' untranslated region. A1CF played a crucial role in cell migration and survival through affecting 3' untranslated region of Dickkopf1 to upregulate its expression in MCF7 cells. PMID: 28639893
47. Circulating sclerostin and Dickkopf-1 levels do not change across the menstrual cycle and do not demonstrate any relationship with estradiol in premenopausal women. PMID: 27601021
48. Results found miR-203 and DKK1 to be expressed at differential levels in cisplatin-sensitive and -insensitive lung adenocarcinoma tissues; there was also a negative correlation between them. PMID: 28350100
49. Serum levels of OPG and DKK-1 were measured in 97 rheumatoid arthritis patients who were treated according to a treat-to-target strategy (T2T) aimed at remission (DAS28<2.6). PMID: 27911913
50. DKK1 can promote vasculogenic mimicry formation via induction of the expression of epithelial-mesenchymal transition and cancer stem-like cell-related proteins. PMID: 27240974

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Secreted.

Dickkopf family

Placenta.

HGNC: 2891

OMIM: 605189

KEGG: hsa:22943

STRING: 9606.ENSP00000363081

UniGene: Hs.40499