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DKK1及其在食管腺癌中的受体：一个有前景的分子靶点。

DKK1 and Its Receptors in Esophageal Adenocarcinoma: A Promising Molecular Target.

作者信息

Despotidis Markos, Lyros Orestis, Driva Tatiana S, Sarantis Panagiotis, Kapetanakis Emmanouil I, Mylonakis Adam, Mamilos Andreas, Sakellariou Stratigoula, Schizas Dimitrios

机构信息

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.

出版信息

Diagnostics (Basel). 2025 Jan 2;15(1):85. doi: 10.3390/diagnostics15010085.

DOI:10.3390/diagnostics15010085
PMID:39795613
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11720708/
Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06e8/11720708/db72f68c02a2/diagnostics-15-00085-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06e8/11720708/3f92bc87a6d9/diagnostics-15-00085-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06e8/11720708/db72f68c02a2/diagnostics-15-00085-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06e8/11720708/3f92bc87a6d9/diagnostics-15-00085-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06e8/11720708/db72f68c02a2/diagnostics-15-00085-g002.jpg

相似文献

[1]
DKK1 and Its Receptors in Esophageal Adenocarcinoma: A Promising Molecular Target.

Diagnostics (Basel). 2025-1-2

[2]
Dickkopf-1 (DKK1) promotes tumor growth via Akt-phosphorylation and independently of Wnt-axis in Barrett's associated esophageal adenocarcinoma.

Am J Cancer Res. 2019-2-1

[3]
Dickkopf-related protein 1/cytoskeleton-associated protein 4 signaling activation by -induced activator protein-1 promotes gastric tumorigenesis the PI3K/AKT/mTOR pathway.

World J Gastroenterol. 2022-12-21

[4]
DKK1 Activates the PI3K/AKT Pathway via CKAP4 to Balance the Inhibitory Effect on Wnt/β-Catenin Signaling and Regulates Wnt3a-Induced MSC Migration.

Stem Cells. 2024-6-14

[5]
Activation of the Dickkopf1-CKAP4 pathway is associated with poor prognosis of esophageal cancer and anti-CKAP4 antibody may be a new therapeutic drug.

Oncogene. 2018-3-22

[6]
Wnt/β-Catenin Signaling Activation beyond Robust Nuclear β-Catenin Accumulation in Nondysplastic Barrett's Esophagus: Regulation via Dickkopf-1.

Neoplasia. 2015-7

[7]
Dynamic palmitoylation controls the microdomain localization of the DKK1 receptors CKAP4 and LRP6.

Sci Signal. 2019-11-19

[8]
Dkk1 involvement and its potential as a biomarker in pancreatic ductal adenocarcinoma.

Clin Chim Acta. 2018-11-16

[9]
The Dickkopf1-cytoskeleton-associated protein 4 axis creates a novel signalling pathway and may represent a molecular target for cancer therapy.

Br J Pharmacol. 2017-7-7

[10]
Opposing Roles of Wnt Inhibitors IGFBP-4 and Dkk1 in Cardiac Ischemia by Differential Targeting of LRP5/6 and β-catenin.

Circulation. 2016-11-1

本文引用的文献

[1]
DKN-01 in Combination With Tislelizumab and Chemotherapy as First-Line Therapy in Advanced Gastric or Gastroesophageal Junction Adenocarcinoma: DisTinGuish.

J Clin Oncol. 2025-1-20

[2]
Newly developed humanized anti-CKAP4 antibody suppresses pancreatic cancer growth by inhibiting DKK1-CKAP4 signaling.

Cancer Sci. 2024-10

[3]
The Multifaceted Role of Human Dickkopf-3 (DKK-3) in Development, Immune Modulation and Cancer.

Cells. 2023-12-29

[4]
Combination therapy of DKK1 inhibition and NKG2D chimeric antigen receptor T cells for the treatment of gastric cancer.

Cancer Sci. 2023-7

[5]
Perioperative FLOT plus ramucirumab for resectable esophagogastric adenocarcinoma: A randomized phase II/III trial of the German AIO and Italian GOIM.

Int J Cancer. 2023-7-1

[6]
CTTN Overexpression Confers Cancer Stem Cell-like Properties and Trastuzumab Resistance via DKK-1/WNT Signaling in HER2 Positive Breast Cancer.

Cancers (Basel). 2023-2-11

[7]
Current Status and Future Prospects for Esophageal Cancer.

Cancers (Basel). 2023-1-26

[8]
DKK1-CKAP4 signal axis promotes hepatocellular carcinoma aggressiveness.

Cancer Sci. 2023-5

[9]
Immunotherapy and Targeted Therapy for Advanced Gastroesophageal Cancer: ASCO Guideline.

J Clin Oncol. 2023-3-1

[10]
Dickkopf-1 drives tumor immune evasion by inducing PD-L1 expression in hepatocellular carcinoma.

Biochem Pharmacol. 2023-2

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