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Dickkopf-3: An Update on a Potential Regulator of the Tumor Microenvironment
SIMPLE SUMMARY: Dkk-3 is a secreted protein with context-dependent functions in several types of cancer. This review focuses on the roles of Dkk-3 in the tumor microenvironment and the effects of modulating Dkk-3 in different settings. ABSTRACT: Dickkopf-3 (Dkk-3) is a member of the Dickkopf family...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9738550/ https://www.ncbi.nlm.nih.gov/pubmed/36497305 http://dx.doi.org/10.3390/cancers14235822 |
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author | Al Shareef, Zainab Ershaid, Mai Nidal Asad Mudhafar, Rula Soliman, Sameh S. M. Kypta, Robert M. |
author_facet | Al Shareef, Zainab Ershaid, Mai Nidal Asad Mudhafar, Rula Soliman, Sameh S. M. Kypta, Robert M. |
author_sort | Al Shareef, Zainab |
collection | PubMed |
description | SIMPLE SUMMARY: Dkk-3 is a secreted protein with context-dependent functions in several types of cancer. This review focuses on the roles of Dkk-3 in the tumor microenvironment and the effects of modulating Dkk-3 in different settings. 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. |
format | Online Article Text |
id | pubmed-9738550 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-97385502022-12-11 Dickkopf-3: An Update on a Potential Regulator of the Tumor Microenvironment Al Shareef, Zainab Ershaid, Mai Nidal Asad Mudhafar, Rula Soliman, Sameh S. M. Kypta, Robert M. Cancers (Basel) Review SIMPLE SUMMARY: Dkk-3 is a secreted protein with context-dependent functions in several types of cancer. This review focuses on the roles of Dkk-3 in the tumor microenvironment and the effects of modulating Dkk-3 in different settings. 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. MDPI 2022-11-25 /pmc/articles/PMC9738550/ /pubmed/36497305 http://dx.doi.org/10.3390/cancers14235822 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Al Shareef, Zainab Ershaid, Mai Nidal Asad Mudhafar, Rula Soliman, Sameh S. M. Kypta, Robert M. Dickkopf-3: An Update on a Potential Regulator of the Tumor Microenvironment |
title | Dickkopf-3: An Update on a Potential Regulator of the Tumor Microenvironment |
title_full | Dickkopf-3: An Update on a Potential Regulator of the Tumor Microenvironment |
title_fullStr | Dickkopf-3: An Update on a Potential Regulator of the Tumor Microenvironment |
title_full_unstemmed | Dickkopf-3: An Update on a Potential Regulator of the Tumor Microenvironment |
title_short | Dickkopf-3: An Update on a Potential Regulator of the Tumor Microenvironment |
title_sort | dickkopf-3: an update on a potential regulator of the tumor microenvironment |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9738550/ https://www.ncbi.nlm.nih.gov/pubmed/36497305 http://dx.doi.org/10.3390/cancers14235822 |
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