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BIOMARKER:

DKK1 overexpression

i
Other names: DKK1, Dickkopf WNT Signaling Pathway Inhibitor 1, Dickkopf-Related Protein 1, SK, Dickkopf (Xenopus Laevis) Homolog 1, Dickkopf 1 Homolog (Xenopus Laevis), Dickkopf-Like Protein 1, Dickkopf 1 Homolog, Dickkopf-1 Like, Dickkopf-1, HDkk-1, DKK-1, Dkk-1
Entrez ID:
2ms
The G-Protein-Coupled Estrogen Receptor Agonist G-1 Mediates Antitumor Effects by Activating Apoptosis Pathways and Regulating Migration and Invasion in Cervical Cancer Cells. (PubMed, Cancers (Basel))
GPER is a promising prognostic marker due to its ability to activate apoptosis and inhibit proliferation without promoting migration/invasion in CC cells. G-1 could potentially be a tool in the treatment of this neoplasia.
Journal
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IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • DKK1 (dickkopf WNT signaling pathway inhibitor 1) • TNFRSF9 (TNF Receptor Superfamily Member 9) • PTGS2 (Prostaglandin-Endoperoxide Synthase 2) • VIM (Vimentin) • FOSL1 (FOS Like 1) • IL1B (Interleukin 1, beta) • PACERR (PTGS2 Antisense NFKB1 Complex-Mediated Expression Regulator RNA)
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DKK1 overexpression • VIM expression
2ms
DKN-01 Suppresses Gastric Cancer Progression Through Activating cGAS-STING Pathway to Block Macrophage M2 Polarization. (PubMed, Appl Biochem Biotechnol)
Moreover, DKN-01 activated the cGAS/STING pathway, while the inactivation of cGAS-STING pathway using RU.521 reversed the inhibition of tumor growth in vivo and macrophage M2 polarization caused by DKN-01. This study reveals that DKN-01 suppresses GC tumor growth through activating cGAS-STING pathway to block macrophage M2 polarization.
Journal
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DKK1 (dickkopf WNT signaling pathway inhibitor 1)
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DKK1 overexpression
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sirexatamab (DKN-01)
8ms
Dickkopf-1 drives perineural invasion via PI3K-AKT signaling pathway in head and neck squamous cancer. (PubMed, MedComm (2020))
In summary, DKK1 can promote the PI3K-AKT signaling pathway in tumor cells and then could induce neuritogenesis and facilitate PNI. MK2206 may be a potential therapeutic target drug for HNSCC patients with PNI.
Journal
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DKK1 (dickkopf WNT signaling pathway inhibitor 1)
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DKK1 overexpression
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MK-2206
1year
Exploring the Role of DKK1 in the Occurrence of Lung Adenocarcinoma Based on the Analysis of Bioinformatics (PubMed, Zhongguo Fei Ai Za Zhi)
High expression of DKK1 in lung adenocarcinoma is associated with poor prognosis. DKK1 is closely associated with tumor immune cell infiltration and pathways. DKK1 can be considered as a potential prognostic marker and a novel target for immunotherapy of lung adenocarcinoma.
Journal • IO biomarker
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DKK1 (dickkopf WNT signaling pathway inhibitor 1)
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DKK1 overexpression
over1year
DKK1 is a predictive biomarker for response to DKN-01: Results of a phase 2 basket study in women with recurrent endometrial carcinoma. (PubMed, Gynecol Oncol)
Collectively, data demonstrates promising clinical activity of a well-tolerated drug, DKN-01, in EC patients with high tumoral DKK1 expression which frequently corresponded to the presence of a Wnt activating mutation. Future development will focus on using DKN-01 in DKK1-high EC patients in combination with immunotherapy.
P2 data • Clinical Trial,Phase II • Journal • IO biomarker • Pan tumor
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DKK1 (dickkopf WNT signaling pathway inhibitor 1)
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DKK1 overexpression
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paclitaxel • sirexatamab (DKN-01)
almost2years
CDK9 inhibitors downregulate DKK1 expression to suppress the metastatic potential of HCC cells. (PubMed, Genes Genomics)
Taken together, our findings suggest that CDK9 inhibitors are potent tools to target DKK1, which can suppress the metastatic progression of HCC.
Journal • Metastases
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CTNNB1 (Catenin (cadherin-associated protein), beta 1) • DKK1 (dickkopf WNT signaling pathway inhibitor 1)
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DKK1 overexpression
almost2years
Dickkopf-1 drives tumor immune evasion by inducing PD-L1 expression in hepatocellular carcinoma. (PubMed, Biochem Pharmacol)
Correlation analysis of human HCC tumor specimens further revealed that DKK1 and PD-L1 expression were positively correlated with p-β-catenin expression. Together, our findings revealed that DKK1 promotes PD-L1 expression through the activation of Akt/β-catenin signaling, providing a potential strategy to enhance the clinical efficacy of PD-1/PD-L1 blockade therapy in HCC patients.
Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • DKK1 (dickkopf WNT signaling pathway inhibitor 1) • CKAP4 (Cytoskeleton Associated Protein 4)
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PD-L1 expression • DKK1 overexpression
over2years
DKK1 drives immune suppressive phenotypes in intrahepatic cholangiocarcinoma and can be targeted with anti-DKK1 therapeutic DKN-01. (PubMed, Liver Int)
DKK1 promotes tumour immune evasion in iCCA through the recruitment of immune suppressive macrophages. Targeting DKK1 with a neutralizing antibody is effective at reducing tumour growth in vivo. As such, DKK1 targeted and immune modulatory therapies may be an effective strategy in iCCA patients with high DKK1 tumour expression or tolerogenic immune phenotypes.
Journal
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DKK1 (dickkopf WNT signaling pathway inhibitor 1) • FOXP3 (Forkhead Box P3)
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DKK1 overexpression
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sirexatamab (DKN-01)
over2years
Convallatoxin suppresses osteosarcoma cell proliferation, migration, invasion, and enhances osteogenic differentiation by downregulating parathyroid hormone receptor 1 (PTHR1) expression and inactivating Wnt/β-catenin pathway. (PubMed, Bioengineered)
Furthermore, PTHR1 overexpression or DKK1 knockdown reversed the suppressing effects of convallatoxin on OS cell proliferation, migration, and invasion, as well as the enhancing effect of convallatoxin on OS cell osteogenic differentiation. Collectively, convallatoxin may repress the malignant progression of OS by blocking PTHR1 and Wnt/β-catenin pathway.
Journal
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DKK1 (dickkopf WNT signaling pathway inhibitor 1) • SPP1 (Secreted Phosphoprotein 1) • RUNX2 (RUNX Family Transcription Factor 2)
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DKK1 overexpression
almost3years
Combination of Wnt/β-Catenin Targets S100A4 and DKK1 Improves Prognosis of Human Colorectal Cancer. (PubMed, Cancers (Basel))
The newly discovered transcriptional cross-regulation of Wnt target S100A4 and Wnt antagonist DKK1 is predominated by an S100A4-induced Wnt signaling feedback loop, increasing cell motility and metastasis risk. S100A4 and DKK1 combination improves the identification of CRC patients at high risk.
Journal
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CTNNB1 (Catenin (cadherin-associated protein), beta 1) • DKK1 (dickkopf WNT signaling pathway inhibitor 1) • S100A4 (S100 calcium binding protein A4)
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DKK1 overexpression
3years
DKK1 Suppresses WWP2 to Enhance Bortezomib Resistance in Multiple Myeloma via Regulating GLI2 Ubiquitination. (PubMed, Carcinogenesis)
Taken together, our findings demonstrate that DKK1 facilitates the generation of bortezomib resistance in MM via downregulating WWP2 and activating Hh pathway. Thus, the manipulation of DKK1-WWP2-GLI2 axis might sensitize myeloma cells to proteasome inhibitors.
Journal
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DKK1 (dickkopf WNT signaling pathway inhibitor 1) • GLI2 (GLI Family Zinc Finger 2)
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DKK1 overexpression
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bortezomib
over3years
Effect of Dickkopf-1 (Dkk-1) and SP600125, a JNK Inhibitor, on Wnt Signaling in Canine Prostate Cancer Growth and Bone Metastases. (PubMed, Vet Sci)
Mice bearing intratibial tumors had increased radiographic density of the intramedullary new bone, large foci of osteolysis, and increased cortical lysis with abundant periosteal new bone formation. Finally, SP600125 has the potential to serve as an alternative adjuvant therapy in some early-stage PCa patients, especially those with high Dkk-1 expression.
Journal
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DKK1 (dickkopf WNT signaling pathway inhibitor 1)
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DKK1 overexpression
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SP600125
over3years
miR-33a-5p inhibits the progression of esophageal cancer through the DKK1-mediated Wnt/β-catenin pathway. (PubMed, Aging (Albany NY))
Thus, we concluded that miR-33a-5p inhibited the progression of EC through the DKK1-mediated Wnt/β-catenin pathway. MiR-33a-5p and DKK1 can be used as potential therapeutic targets of EC.
Journal
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DKK1 (dickkopf WNT signaling pathway inhibitor 1)
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DKK1 overexpression
over3years
AXL Overexpression in Tumor-Derived Endothelial Cells Promotes Vessel Metastasis in Patients With Hepatocellular Carcinoma. (PubMed, Front Oncol)
R428 reduced tumor growth and CD 31 expression in HCC in PDX xenograft nude mice. Therefore, AXL over-expression in TECs promotes vessel metastasis of HCC, which indicates that AXL in TECs could be a potential therapeutic target in HCC patients with PVTT.
Clinical • Journal
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AXL (AXL Receptor Tyrosine Kinase) • DKK1 (dickkopf WNT signaling pathway inhibitor 1) • SOX2
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DKK1 overexpression • AXL expression • AXL overexpression
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bemcentinib (BGB324)
over3years
The Dickkopf1 and FOXM1 positive feedback loop promotes tumor growth in pancreatic and esophageal cancers. (PubMed, Oncogene)
Although it has been reported that FOXM1 enhances Wnt signaling, FOXM1 induced DKK1 expression independently of Wnt signaling in PDAC and ESCC cells. These results suggest that DKK1 and FOXM1 create a positive feedback loop to promote cancer cell proliferation.
Journal
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DKK1 (dickkopf WNT signaling pathway inhibitor 1) • FOXM1 (Forkhead Box M1)
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DKK1 overexpression
over3years
Andrographis overcomes 5-fluorouracil associated chemoresistance through inhibition of DKK1 in colorectal cancer. (PubMed, Carcinogenesis)
In line with in vitro findings, andrographis enhanced 5FU-induced anti-cancer activity in mice xenografts and patient-derived tumoroids (p<0.01). In conclusion, our data provide novel evidence for andrographis-mediated reversal of 5FU resistance, highlighting its potential role as an adjunct to conventional chemotherapy in CRC.
Journal
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DKK1 (dickkopf WNT signaling pathway inhibitor 1)
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DKK1 overexpression
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5-fluorouracil
almost4years
Dkk1 inhibits malignant transformation induced by Bmi1 via the β-catenin signaling axis in WB-F344 oval cells. (PubMed, FEBS Open Bio)
Finally, we used transcriptome sequencing to perform a comprehensive evaluation of the transcriptome-related changes in WB-F344 oval cells induced by Dkk1 and Bmi1. These results may provide evidence for future studies of the pathogenesis of hepatocellular carcinoma and the design of possible therapies.
Journal
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DKK1 (dickkopf WNT signaling pathway inhibitor 1) • BMI1 (BMI1 proto-oncogene, polycomb ring finger)
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DKK1 overexpression
almost4years
Free CA125 promotes ovarian cancer cell migration and tumor metastasis by binding Mesothelin to reduce DKK1 expression and activate the SGK3/FOXO3 pathway. (PubMed, Int J Biol Sci)
These experiments revealed that the SGK3/FOXO3 pathway was activated, wherein decreased expression of DKK1 was caused by CA125, which fuels ovarian cancer cell migration. Mesothelin is a potential therapeutic target for the treatment of ovarian cancer metastasis.
Journal
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MSLN (Mesothelin) • MUC16 (Mucin 16, Cell Surface Associated) • DKK1 (dickkopf WNT signaling pathway inhibitor 1)
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DKK1 overexpression
almost4years
Hypoxia-induced CREB cooperates MMSET to modify chromatin and promote DKK1 expression in multiple myeloma. (PubMed, Oncogene)
Combined treatment with a CREB inhibitor and the hypoxia-activated prodrug TH-302 (evofosfamide) significantly reduced MM-induced bone destruction in vivo. Taken together, our findings reveal that hypoxia and a cytogenetic abnormality regulate DKK1 expression in myeloma cells, and provide an additional rationale for the development of therapeutic strategies that interrupt DKK1 to cure MM.
Journal
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DKK1 (dickkopf WNT signaling pathway inhibitor 1)
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Chr t(4;14) • DKK1 overexpression
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evofosfamide (IMGS-101)
4years
Small GTPase RAB6 deficiency promotes alveolar progenitor cell renewal and attenuates PM2.5-induced lung injury and fibrosis. (PubMed, Cell Death Dis)
Furthermore, DKK1 inhibitors promoted proliferation, self-renewal and wnt/β-catenin signaling of RAB6 overexpressing AEC2 cells, and attenuated PM2.5-induced pulmonary fibrosis in mice. These data establish RAB6 as a regulator of DKK1 autocrine and wnt/β-catenin signal that serves to regulate AEC2 cell proliferation and self-renewal, and suggest a mechanism that RAB6 disruption may promote AEC2 cell proliferation and self-renewal to enhance lung repair following PM2.5 injury.
Journal
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DKK1 (dickkopf WNT signaling pathway inhibitor 1)
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DKK1 overexpression
over4years
LncRNA Linc-PINT inhibits miR-523-3p to hamper retinoblastoma progression by upregulating Dickkopf-1 (DKK1). (PubMed, Biochem Biophys Res Commun)
Finally, Linc-PINT inhibited tumorigenicity of RB cells in xenograft mice models. In general, analysis of the data suggested that Linc-PINT inhibited miR-523-3p to upregulate DKK1, resulting in the inhibition of RB, and we demonstrated that Linc-PINT and miR-523-3p could be utilized as potential diagnostic and therapeutic biomarkers for RB in clinic.
Journal
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DKK1 (dickkopf WNT signaling pathway inhibitor 1)
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DKK1 overexpression
over4years
Prognostic role of dickkopf-1 in patients with cancer. (PubMed, Medicine (Baltimore))
In stratified analyzes, the higher expression of DKK1 could reduced the OS in patients with breast cancer,digestive system cancer and urogenital system cancer, but not patients with the lung cancer. It also showed that higher expression of DKK1 was significantly associated with shorter progression-free survival, disease-free survival and time to recurrence in cancer patients.The present study indicate that higher expression of DKK1 predict an unfavorable clinical outcome in patients with breast cancer, digestive system cancer and urogenital system cancer.
Clinical • Journal
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DKK1 (dickkopf WNT signaling pathway inhibitor 1)
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DKK1 overexpression
over4years
SMURF1-mediated ubiquitination of ARHGAP26 promotes ovarian cancer cell invasion and migration. (PubMed, Exp Mol Med)
ARHGAP26 upregulation in SKOV3 cells significantly inhibited SMURF1 upregulation-induced cell migration and invasion. Overall, SMURF1-mediated ubiquitination of ARHGAP26 may promote invasion and migration of ovarian cancer cells via the β-catenin pathway.
Journal
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CTNNB1 (Catenin (cadherin-associated protein), beta 1) • DKK1 (dickkopf WNT signaling pathway inhibitor 1) • MMP2 (Matrix metallopeptidase 2) • MMP7 (Matrix metallopeptidase 7)
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DKK1 overexpression
over4years
Hypoxic postconditioning activates the Wnt/β-catenin pathway and protects against transient global cerebral ischemia through Dkk1 Inhibition and GSK-3β inactivation. (PubMed, FASEB J)
Finally, the administration of LY294002, an inhibitor of PI3K, increased GSK-3β activity and blocked nuclear β-catenin accumulation, thereby decreasing survivin expression and elevating the Bax-to-Bcl-2 ratio after HPC. These results suggest that activation of the Wnt/β-catenin pathway through Dkk1 inhibition and PI3K/protein kinase B pathway-mediated GSK-3β inactivation contributes to the neuroprotection of HPC against tGCI.-Zhan, L., Liu, D., Wen, H., Hu, J., Pang, T., Sun, W., Xu, E. Hypoxic postconditioning activates the Wnt/β-catenin pathway and protects against transient global cerebral ischemia through Dkk1 inhibition and GSK-3β inactivation.
Clinical • Journal
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BCL2 (B-cell CLL/lymphoma 2) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • DKK1 (dickkopf WNT signaling pathway inhibitor 1) • BIRC5 (Baculoviral IAP repeat containing 5)
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DKK1 overexpression
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LY294002
over4years
Analyzing the prognostic value of DKK1 expression in human cancers based on bioinformatics. (PubMed, Ann Transl Med)
The bioinformatics analysis revealed a significant overexpression of DKK1 in HNSC, LUSC, and PAAD, with DKK1 overexpression being associated with adverse outcome in these patients, but how DKK1 expression levels relate to hematological malignancies and prognosis is still unclear. These new insights into the function of DKK1 may provide a basis for new targeted drug therapy and an avenue for further investigation into the mechanisms underlying carcinogenesis of DKK1 in different cancer types.
Journal
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DKK1 (dickkopf WNT signaling pathway inhibitor 1)
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DKK1 overexpression