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Updated: Mar 2, 2026

Characterization of Cell Membrane Extensions and Studying Their Roles in Cancer Cell Adhesion Dynamics
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The Dickkopf1-cytoskeleton-associated protein 4 axis creates a novel signalling pathway and may represent a molecular

Akira Kikuchi1, Katsumi Fumoto1, Hirokazu Kimura1

  • 1Department of Biochemistry and Molecular Biology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.

British Journal of Pharmacology
|May 18, 2017
PubMed

Insights

Dickkopf 1 (DKK1) binds to its novel receptor, cytoskeleton-associated protein 4 (CKAP4), to promote cancer cell proliferation. Targeting the DKK1-CKAP4 axis may offer new cancer therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signalling

Background:

  • Dickkopf 1 (DKK1) antagonizes Wnt signalling but also promotes tumour aggressiveness.
  • The mechanism of DKK1-driven cancer cell proliferation was previously unclear.
  • Cytoskeleton-associated protein 4 (CKAP4) is identified as a novel DKK1 receptor.

Purpose of the Study:

  • To elucidate the mechanism of DKK1-mediated cancer cell proliferation.
  • To investigate the role of CKAP4 as a DKK1 receptor.
  • To evaluate the DKK1-CKAP4 axis as a potential therapeutic target.

Main Methods:

  • Investigated DKK1-CKAP4 interaction and downstream signalling.
  • Assessed CKAP4 expression in tumour samples.
  • Utilized CKAP4 knockdown and anti-CKAP4 antibody treatment in preclinical models.

Main Results:

  • DKK1 binding to cell surface CKAP4 stimulates cancer cell proliferation.
  • DKK1-CKAP4 complex formation activates the PI3K/Akt pathway.
  • High DKK1 and CKAP4 expression correlates with poor prognosis in pancreatic and lung cancers.
  • CKAP4 inhibition suppresses tumour growth in vivo.

Conclusions:

  • The DKK1-CKAP4 signalling axis drives cancer proliferation.
  • CKAP4 is a viable therapeutic target for DKK1- and CKAP4-expressing cancers.
  • Targeting this pathway holds promise for future cancer drug development.

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