Despotidis Markos, Lyros Orestis, Driva Tatiana S, Sarantis Panagiotis, Kapetanakis Emmanouil I, Mylonakis Adam, Mamilos Andreas, Sakellariou Stratigoula, Schizas Dimitrios
First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece.
Fourth Department of Surgery, Attikon University Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece.
Diagnostics (Basel). 2025 Jan 2;15(1):85. doi: 10.3390/diagnostics15010085.
Esophageal adenocarcinoma (EAC) is an aggressive gastrointestinal (GI) malignancy with increasing incidence. Despite the recent progress in targeted therapies and surgical approaches, the survival rates of esophageal adenocarcinoma patients remain poor. The Dickkopf (DKK) proteins are secretory proteins known mainly as antagonists of the Wnt/β-catenin signaling pathway, which is considered an oncogene. However, it has been shown that in several GI cancers, including esophageal cancer, DKK1 may act as an oncogene itself through Wnt-independent signaling pathways. LRP5\6 and Kremen1/2 (Krm1/2) are transmembrane receptors to which the DKK proteins are mainly known to bind. CKAP4 (cytoskeleton-associated protein 4) is a novel receptor of DKK1, and the DKK1-CKAP4 pathway seems to be crucial in the role of DKK1 as an oncogene. The aim of this review is to feature the essential role of DKK1 and its receptors in carcinogenesis with a focus on EAC in an era of urgent need for specific biomarkers along with improved targeted therapies.
食管腺癌（EAC）是一种侵袭性的胃肠道（GI）恶性肿瘤，其发病率呈上升趋势。尽管近年来在靶向治疗和手术方法方面取得了进展，但食管腺癌患者的生存率仍然很低。Dickkopf（DKK）蛋白是分泌蛋白，主要作为Wnt/β-连环蛋白信号通路的拮抗剂，该信号通路被认为是一种致癌基因。然而，研究表明，在包括食管癌在内的几种胃肠道癌症中，DKK1可能通过非Wnt信号通路本身发挥致癌基因的作用。LRP5\6和Kremen1/2（Krm1/2）是已知的DKK蛋白主要结合的跨膜受体。CKAP4（细胞骨架相关蛋白4）是DKK1的一种新型受体，DKK1-CKAP4通路似乎在DKK1作为致癌基因的作用中至关重要。这篇综述的目的是在迫切需要特异性生物标志物以及改进靶向治疗的时代，重点介绍DKK1及其受体在致癌过程中的重要作用，特别是在食管腺癌中的作用。
