Department of Biomedical Sciences, Mercer University School of Medicine, Savannah, GA 31404, USA.
Department of Biomedical Sciences, Mercer University School of Medicine, Savannah, GA 31404, USA; Department of Histology and Embryology, Shantou University Medical College, Shantou 515000, China.
Clin Chim Acta. 2019 Jan;488:226-234. doi: 10.1016/j.cca.2018.11.023. Epub 2018 Nov 16.
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.
Dickkopf-1（Dkk1）的失调与多种癌症的发病机制有关。它是 Dkk 家族蛋白的一部分，包括 Dkk2、Dkk3 和 Dkk4。这个家族的分泌蛋白具有相似的保守半胱氨酸结构域，通过引起蛋白酶体 B-连环蛋白降解、诱导细胞凋亡和阻止细胞增殖来抑制 Wnt/b-连环蛋白途径。胰腺导管腺癌（PDAC）是美国第四大癌症死亡原因，因为诊断晚期和当前治疗效果有限。在 PADC 患者的标本和血清中发现 Dkk1 增加。Dkk1 可以作为 PDAC 的有前途的生物标志物，通过与当前生物标志物金标准相比，提高早期检测和监测进展的能力，从而有可能提高 PDAC 的生存率。此外，最近的研究表明，Dkk1 可能是癌症免疫治疗的一个极好的靶点。有趣的是，Dkk1-CKAP4-PI3K/AKT 信号通路也在胰腺癌细胞增殖中发挥作用。在这篇综述中，我们目前研究了 Dkk1 在 PDAC 中的多种机制，并探讨了其在妇科癌症中的功能、调节作用及其临床应用，包括胰腺导管腺癌（PDAC）、乳腺癌、卵巢癌、宫颈癌和子宫内膜癌。对 Dkk1 机制的进一步研究及其作为诊断工具的单独或与其他生物标志物联合使用，可能在临床上有助于更好地理解 PDAC 的病理学并改善其早期检测和治疗。
