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

• Published in: Clinica chimica acta 2019-01, Vol.488, p.226-234
• Main Authors: Igbinigie, Eseosaserea, Guo, Fengbiao, Jiang, Shi-Wen, Kelley, Cullen, Li, Jinping
• Format: Article
• Language: English
• Subjects: Apoptosis; Biomarker; Biomarkers, Tumor - blood; Biomarkers, Tumor - metabolism; Carcinoma, Pancreatic Ductal - diagnosis; Carcinoma, Pancreatic Ductal - drug therapy; Carcinoma, Pancreatic Ductal - metabolism; Cell Proliferation; CKAP4/PI3K/AKT pathway; Dkk1; Humans; Intercellular Signaling Peptides and Proteins - blood; Intercellular Signaling Peptides and Proteins - metabolism; Pancreatic ductal adenocarcinoma (PDAC); Pancreatic Neoplasms - diagnosis; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - metabolism; Serum; Wnt signaling pathway
• ISSN: 0009-8981; 1873-3492
• DOI: 10.1016/j.cca.2018.11.023

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. •Dkk1 is overexpressed in PDAC and could be a potential biomarker with a sensitivity of 89.3% and specificity 79.3%.•High serum levels of Dkk1 make it a promising diagnostic tool for early detection and/or monitoring progression of PDAC.•CKAP4, a Dkk1 receptor, can promote pancreatic cancer cell proliferation through the PI3K/AKT signaling pathway.