Dickkopf-3: an update on a potential regulator of the tumor microenvironment

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Title: Dickkopf-3: an update on a potential regulator of the tumor microenvironment
Authors: Al Shareef, Z
Ershaid, MNA
Mudhafar, R
Soliman, SSM
Kypta, RM
Item Type: Journal Article
Abstract: Dickkopf-3 (Dkk-3) is a member of the Dickkopf family protein of secreted Wingless-related integration site (Wnt) antagonists that appears to modulate regulators of the host microenvironment. In contrast to the clear anti-tumorigenic effects of Dkk-3-based gene therapies, the role of endogenous Dkk-3 in cancer is context-dependent, with elevated expression associated with tumor promotion and suppression in different settings. The receptors and effectors that mediate the diverse effects of Dkk-3 have not been characterized in detail, contributing to an ongoing mystery of its mechanism of action. This review compares the various functions of Dkk-3 in the tumor microenvironment, where Dkk-3 has been found to be expressed by subpopulations of fibroblasts, endothelial, and immune cells, in addition to epithelial cells. We also discuss how the activation or inhibition of Dkk-3, depending on tumor type and context, might be used to treat different types of cancers.
Issue Date: 1-Dec-2022
Date of Acceptance: 16-Nov-2022
DOI: 10.3390/cancers14235822
ISSN: 2072-6694
Publisher: MDPI AG
Start Page: 1
End Page: 16
Journal / Book Title: Cancers
Volume: 14
Issue: 23
Copyright Statement: Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (
Publication Status: Published
Article Number: ARTN 5822
Online Publication Date: 2022-11-25
Appears in Collections:Department of Surgery and Cancer

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