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

Markos Despotidis1, Orestis Lyros2, Tatiana S Driva3

  • 1First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece.

Diagnostics (Basel, Switzerland)
|January 11, 2025
PubMed

Insights

Dickkopf-1 (DKK1) may drive esophageal adenocarcinoma (EAC) through novel pathways, independent of Wnt signaling. Targeting DKK1 and its receptors like CKAP4 could offer new therapeutic strategies for this aggressive cancer.

Area of Science:

  • Gastroenterology
  • Oncology
  • Molecular Biology

Background:

  • Esophageal adenocarcinoma (EAC) is an aggressive cancer with poor survival rates.
  • Dickkopf (DKK) proteins typically inhibit Wnt/β-catenin signaling but can promote cancer via Wnt-independent pathways.
  • The Dickkopf-1 (DKK1) and its novel receptor, cytoskeleton-associated protein 4 (CKAP4), pathway is implicated in gastrointestinal cancers.

Purpose of the Study:

  • To review the role of DKK1 and its receptors in carcinogenesis, focusing on EAC.
  • To highlight the DKK1-CKAP4 pathway's oncogenic function in EAC.
  • To emphasize the need for specific biomarkers and targeted therapies for EAC.

Main Methods:

  • Literature review of DKK1, its receptors (LRP5/6, Kremen1/2, CKAP4), and their role in EAC.
  • Analysis of Wnt-dependent and Wnt-independent signaling pathways involving DKK1.
  • Exploration of the DKK1-CKAP4 interaction in cancer progression.

Main Results:

  • DKK1 can act as an oncogene in EAC through Wnt-independent mechanisms.
  • The DKK1-CKAP4 pathway represents a novel oncogenic signaling axis in EAC.
  • Established DKK1 receptors (LRP5/6, Krm1/2) and the novel CKAP4 receptor are involved.

Conclusions:

  • DKK1 and its interaction with CKAP4 are critical in EAC development and progression.
  • The DKK1-CKAP4 pathway presents a potential therapeutic target for EAC.
  • Further research into DKK1-mediated signaling is crucial for developing novel EAC biomarkers and treatments.
Keywords:
DKK proteinsDKK receptorsWnt signaling pathwayesophageal adenocarcinomamolecular target

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