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

British Journal of Pharmacology
Akira KikuchiHirokazu Kimura

Abstract

Dickkopf 1 (DKK1) is a secreted protein and antagonizes oncogenic Wnt signalling by binding to the Wnt co-receptor, low-density lipoprotein receptor-related protein 6. DKK1 has also been suggested to regulate its own signalling, associated with tumour aggressiveness. However, the underlying mechanism by which DKK1 promotes cancer cell proliferation has remained to be clarified for a long time. The cytoskeleton-associated protein 4 (CKAP4), originally identified as an endoplasmic reticulum membrane protein, was recently found to act as a novel DKK1 receptor. DKK1 stimulates cancer cell proliferation when CKAP4 is expressed on the cell surface membrane. Although there are no tyrosine residues in the intracellular region of CKAP4, CKAP4 forms a complex with PI3K upon the binding of DKK1, leading to the activation of Akt. Both DKK1 and CKAP4 are frequently expressed in pancreatic and lung tumours, and their simultaneous expression is negatively correlated with prognosis. Knockdown of CKAP4 in cancer cells and treatment of mice with the anti-CKAP4 antibody inhibit Akt activity in cancer cells and suppress xenograft tumour formation, suggesting that CKAP4 may represent a therapeutic target for cancers expressing both DKK1 and CKAP4. ...Continue Reading

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Dec 3, 2017·Molecular & Cellular Proteomics : MCP·Rupert L MayerChristopher Gerner
Dec 14, 2017·British Journal of Pharmacology·Gunnar Schulte, Vitezslav Bryja
Jun 5, 2019·Molecular and Cellular Biology·Yoshihito OsugiAkira Kikuchi
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Jan 6, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Hirokazu KimuraAkira Kikuchi
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Feb 23, 2021·Frontiers in Molecular Biosciences·Shuang-Xi LiZhi-Yong Guo
Jun 22, 2019·Differentiation; Research in Biological Diversity·Wook-Jin Chae, Alfred L M Bothwell

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