Creative Biogene Creative Biogene
Inquiry
Pages
Products
  1. Home
  2. Search Results for "DKK1"

DKK1

Official Full Name
dickkopf WNT signaling pathway inhibitor 1
Organism
Homo sapiens
GeneID
22943
Background
This gene encodes a member of the dickkopf family of proteins. Members of this family are secreted proteins characterized by two cysteine-rich domains that mediate protein-protein interactions. The encoded protein binds to the LRP6 co-receptor and inhibits beta-catenin-dependent Wnt signaling. This gene plays a role in embryonic development and may be important in bone formation in adults. Elevated expression of this gene has been observed in numerous human cancers and this protein may promote proliferation, invasion and growth in cancer cell lines. [provided by RefSeq, Sep 2017]
Synonyms
SK; DKK-1;
Bio Chemical Class
Dickkopf protein
Protein Sequence
MMALGAAGATRVFVAMVAAALGGHPLLGVSATLNSVLNSNAIKNLPPPLGGAAGHPGSAVSAAPGILYPGGNKYQTIDNYQPYPCAEDEECGTDEYCASPTRGGDAGVQICLACRKRRKRCMRHAMCCPGNYCKNGICVSSDQNHFRGEIEETITESFGNDHSTLDGYSRRTTLSSKMYHTKGQEGSVCLRSSDCASGLCCARHFWSKICKPVLKEGQVCTKHRRKGSHGLEIFQRCYCGEGLSCRIQKDHHQASNSSRLHTCQRH
Open
Disease
Biliary tract cancer, Endometrial cancer, Esophageal cancer, Liver cancer, Low bone mass disorder, Multiple myeloma, Oesophagogastric junction cancer, Ovarian cancer, Prostate cancer
Approved Drug
0
Clinical Trial Drug
3 +
Discontinued Drug
0

Cat.No. Product Name Price
Cat.No. Product Name Price
Cat.No. Product Name Price
Cat.No. Product Name Tag Price
Cat.No. Product Name Price

Detailed Information

Dickkopf-related protein 1 (DKK1) belongs to the DKK family and inhibits the Wnt/β-catenin signaling pathway. The DKK1 gene is found on human chromosome 10q11.2 and encodes a secretory glycoprotein weighing about 28.7 kDa and containing 266 amino acids. The molecular structure of DKK1 is complicated, including an N-terminal signal sequence, two cysteine-rich conserved regions (Dkk_N and an auxiliary lipase fold area), and a C-terminal glycosylation site. The N-terminal signal sequence largely drives DKK1 to the endoplasmic reticulum (ER). It regulates secretion, whereas the cysteine-rich sections stabilize the protein via disulfide bonds and bind to the Wnt receptors LRP5/6 and Kremen1/2. DKK1 regulates intracellular and extracellular signal transduction via these structural properties.

Figure 1 describes the role of DKK1 in regulating various signaling pathways, including the inhibition of canonical Wnt signaling, activation of PI3K/Akt signaling, and activation of the JNK pathway.Figure 1. DKK1 plays a versatile role in cell signaling by inhibiting Wnt signaling and promoting alternative pathways that influence cell proliferation and differentiation. (Jiang H, et al., 2022)

Role of DKK1 in the Wnt/β-catenin Signaling Pathway

The Wnt/β-catenin signaling system regulates cell proliferation, differentiation, and survival. Wnt proteins activate Dishevelled (Dvl) by binding to Frizzled (Fz) and LRP5/6 receptors, blocking the formation of the destruction complex. This stabilizes β-catenin and allows it to translocate to the nucleus to control transcription of downstream target genes. However, as an antagonist of Wnt signaling, DKK1 suppresses this pathway via two mechanisms:

1. Competitive Binding to the LRP5/6 Receptor: DKK1 competes with Wnt proteins for binding sites on LRP5/6, limiting the beginning of Wnt signaling.

2. Induction of LRP5/6 Endocytosis: By establishing a complex with Kremen1/2, DKK1 increases LRP5/6 endocytosis and degradation, decreasing signal transmission.

DKK1 inhibits β-catenin stability and nuclear translocation, affecting downstream gene expression and biological processes such as cell proliferation, differentiation, and death.

Expression and Functional Characteristics of DKK1

DKK1 is present in a broad range of tissues and cell types, including bone tissue, the placenta, skin, the prostate, and the kidney. DKK1 suppresses bone formation in osteoblasts and osteocytes while activating bone resorption via the Wnt/β-catenin signaling pathway. In recent years, the involvement of DKK1 in cancers, aberrant growth and development, and different disorders has received a lot of attention. According to research, DKK1 expression and activity vary depending on the cellular environment and pathological state, functioning as an oncogene in certain cancers while inhibiting malignancies in others.

Role of DKK1 in Tumors

In multiple myeloma, increased DKK1 expression is associated with bone damage. It suppresses the development of bone marrow stem cells into osteoblasts, hence boosting bone resorption. The development of anti-DKK1 antibodies and vaccines has shown promise for treating multiple myeloma. Anti-DKK1 vaccinations, for example, may stimulate particular T-cell responses that suppress myeloma cell proliferation and bone damage.

DKK1 is abundantly expressed in gastric cancer cells and has been associated with enhanced invasiveness and tumor spread. Clinical studies show that Sirexatamab, a targeted medication against DKK1, may block angiogenesis while activating immune-related proteins such IFNγ, IL-15, and IL-33. This enhances tumor cell killing and improves patient prognosis.

In colorectal cancer, DKK1 suppresses the creation of vasculogenic mimicry (VM), which prevents the tumor blood supply from expanding. VM is a pseudo-vascular structure generated by tumor cells under appropriate circumstances that provides nutrition while also encouraging invasion and metastasis. DKK1 overexpression dramatically inhibits colorectal cancer cells' capacity to produce VM, indicating that it might be a therapeutic target in cancer.

In breast cancer, DKK1 may control the disease by regulating bone metastases or accelerate tumor growth by increasing angiogenesis and cell migration. Similarly, in pancreatic cancer, detecting both DKK1 and the serum tumor marker CA19-9 may increase diagnostic accuracy and act as a specific signal for disease progression.

Role of DKK1 in Other Diseases

Beyond its role in tumors, DKK1 is involved in the pathophysiology of various non-tumorous diseases. In Parkinson's disease models, DKK1 knockdown significantly reduces neuronal apoptosis and improves neuronal survival. Additionally, in osteoporosis and ankylosing spondylitis, DKK1 exacerbates the disruption of bone homeostasis by inhibiting osteoblast differentiation and activating osteoclast activity.

Clinical Research and Drug Development Targeting DKK1

Given DKK1's crucial role in various diseases, targeting this protein has become a focal point in drug development. BHQ-880 and Sirexatamab, as DKK1 inhibitors, have entered clinical trials for multiple myeloma and gastric cancer. Furthermore, DKK1-related vaccines and monoclonal antibodies are under exploration. Sirexatamab, for example, has shown strong therapeutic results in clinical trials of gastric cancer, with effectiveness closely related to DKK1 expression levels in patient tumors. These developments not only open up new avenues for targeted therapeutics against DKK1, but also set the basis for a better understanding of DKK1's mechanisms of action.

References:

  1. Jiang H, Zhang Z, et al. Drug Discovery of DKK1 Inhibitors. Front Pharmacol. 2022 Mar 9;13:847387.
  2. Bley IA, Zwick A, et al. DKK1 inhibits canonical Wnt signaling in human papillomavirus-positive penile cancer cells. Transl Oncol. 2022 Jan;15(1):101267.
  3. Igbinigie E, Guo F, et al. Dkk1 involvement and its potential as a biomarker in pancreatic ductal adenocarcinoma. Clin Chim Acta. 2019 Jan;488:226-234.
Quick Inquiry

Interested in learning more?

Contact us today for a free consultation with the scientific team and discover how Creative Biogene can be a valuable resource and partner for your organization.

Request a quote today!

Inquiry

Products

Transfected Stable Cell Lines

Premade Virus Particles

Laboratory Equipment

RNA Interference Products

Cell Lysate

Clones

Enzymes

Kits

Aptamers

Services

Stable Cell Line Generation

Target-based Drug Discovery Service

Custom Libraries Construction Service

Microbe Genome Editing Service

Biosafety Testing Service

Nucleotides Service

MicroRNA Service

RNAi Service

Custom Viral Service

Platforms

CRISPR/Cas9 PlatformCB

QvirusTM Platform

IntegrateRNA Platform

Microbiology Platform

Zebrafish Platform

Get in Touch

Tel

Fax

Email

USA

Germany

Copyright © Creative Biogene. All rights reserved.

Privacy Policy | Cookie Policy