Dkk1 involvement and its potential as a biomarker in pancreatic ductal adenocarcinoma.

Abstract

Dickkopf-1 (Dkk1)'s dysregulation has been implicated in the pathogenesis of a variety of cancers. It is part of the Dkk family of proteins that includes Dkk2, Dkk3 and Dkk4. This family of secreted proteins shares similar conserved cysteine domains and inhibits the Wnt/b-catenin pathway by causing proteasomal B-catenin degradation, inducing apoptosis, and preventing cell proliferation. Pancreatic ductal adenocarcinoma (PDAC) is the 4th leading cause of cancer mortality in the United States due to the late stage of diagnosis and the limited effectiveness of current therapy. Dkk1 is found increased in PADC patients' specimens and serum. Dkk1 can be a promising biomarker specific to PDAC, which has the potential to increase PDAC survival rates through improving early stage detection and monitoring progression compared to current biomarker gold standards. In addition, recent studies suggest that Dkk1 could be an excellent target for cancer immunotherapy. Interestingly, Dkk1-CKAP4-PI3K/AKT signal pathway also plays role in pancreatic cancer cell proliferation. In this review, we present the multiple mechanisms of Dkk1 in PDAC studied thus far and explore its function, regulation, and clinical applications in gynecological cancers including pancreatic ductal adenocarcinoma (PDAC), breast, ovarian, cervical, and endometrial cancer. Further research into Dkk1's mechanism and use as a diagnostic tool, alone or in combination with other biomarkers, could prove clinically useful for better understanding the pathology of PDAC and improving its early detection and treatment.

• Authors: Eseosaserea Igbinigie, Fengbiao Guo, Shi-Wen Jiang, Cullen Kelley, Jinping Li
• Journal: Clinica chimica acta; international journal of clinical chemistry (Clin Chim Acta) Vol. 488 Pg. 226-234 (Jan 2019) ISSN: 1873-3492 [Electronic] Netherlands
• PMID: 30452897 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• Biomarkers, Tumor
• DKK1 protein, human
• Intercellular Signaling Peptides and Proteins

Topics

• Apoptosis
• Biomarkers, Tumor (blood, metabolism)
• Carcinoma, Pancreatic Ductal (diagnosis, drug therapy, metabolism)
• Cell Proliferation
• Humans
• Intercellular Signaling Peptides and Proteins (blood, metabolism)
• Pancreatic Neoplasms (diagnosis, drug therapy, metabolism)