DKK1 and Its Receptors in Esophageal Adenocarcinoma: A Promising Molecular Target
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 prot...
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MDPI AG
2025-01-01
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| author | Markos Despotidis Orestis Lyros Tatiana S. Driva Panagiotis Sarantis Emmanouil I. Kapetanakis Adam Mylonakis Andreas Mamilos Stratigoula Sakellariou Dimitrios Schizas |
| author_facet | Markos Despotidis Orestis Lyros Tatiana S. Driva Panagiotis Sarantis Emmanouil I. Kapetanakis Adam Mylonakis Andreas Mamilos Stratigoula Sakellariou Dimitrios Schizas |
| author_sort | Markos Despotidis |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-6842114598784d3ea28229e845327ac5 |
| institution | Kabale University |
| issn | 2075-4418 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Diagnostics |
| spelling | doaj-art-6842114598784d3ea28229e845327ac52025-01-10T13:16:40ZengMDPI AGDiagnostics2075-44182025-01-011518510.3390/diagnostics15010085DKK1 and Its Receptors in Esophageal Adenocarcinoma: A Promising Molecular TargetMarkos Despotidis0Orestis Lyros1Tatiana S. Driva2Panagiotis Sarantis3Emmanouil I. Kapetanakis4Adam Mylonakis5Andreas Mamilos6Stratigoula Sakellariou7Dimitrios Schizas8First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, GreeceFourth Department of Surgery, Attikon University Hospital, National and Kapodistrian University of Athens, 12462 Athens, GreeceFirst Department of Pathology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, GreeceDepartment of Biological Chemistry, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, GreeceDepartment of Thoracic Surgery, Attikon University Hospital, National and Kapodistrian University of Athens, 12462 Athens, GreeceFirst Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, GreeceInstitute of Pathology, University of Regensburg, 93053 Bavaria, GermanyFirst Department of Pathology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, GreeceFirst Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, GreeceEsophageal 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.https://www.mdpi.com/2075-4418/15/1/85esophageal adenocarcinomaDKK proteinsDKK receptorsWnt signaling pathwaymolecular target |
| spellingShingle | Markos Despotidis Orestis Lyros Tatiana S. Driva Panagiotis Sarantis Emmanouil I. Kapetanakis Adam Mylonakis Andreas Mamilos Stratigoula Sakellariou Dimitrios Schizas DKK1 and Its Receptors in Esophageal Adenocarcinoma: A Promising Molecular Target Diagnostics esophageal adenocarcinoma DKK proteins DKK receptors Wnt signaling pathway molecular target |
| title | DKK1 and Its Receptors in Esophageal Adenocarcinoma: A Promising Molecular Target |
| title_full | DKK1 and Its Receptors in Esophageal Adenocarcinoma: A Promising Molecular Target |
| title_fullStr | DKK1 and Its Receptors in Esophageal Adenocarcinoma: A Promising Molecular Target |
| title_full_unstemmed | DKK1 and Its Receptors in Esophageal Adenocarcinoma: A Promising Molecular Target |
| title_short | DKK1 and Its Receptors in Esophageal Adenocarcinoma: A Promising Molecular Target |
| title_sort | dkk1 and its receptors in esophageal adenocarcinoma a promising molecular target |
| topic | esophageal adenocarcinoma DKK proteins DKK receptors Wnt signaling pathway molecular target |
| url | https://www.mdpi.com/2075-4418/15/1/85 |
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