Cargando…
WNT Signaling in Tumors: The Way to Evade Drugs and Immunity
WNT/β-catenin signaling is involved in many physiological processes. Its implication in embryonic development, cell migration, and polarization has been shown. Nevertheless, alterations in this signaling have also been related with pathological events such as sustaining and proliferating the cancer...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934036/ https://www.ncbi.nlm.nih.gov/pubmed/31921125 http://dx.doi.org/10.3389/fimmu.2019.02854 |
_version_ | 1783483328995786752 |
---|---|
author | Martin-Orozco, Elena Sanchez-Fernandez, Ana Ortiz-Parra, Irene Ayala-San Nicolas, Maria |
author_facet | Martin-Orozco, Elena Sanchez-Fernandez, Ana Ortiz-Parra, Irene Ayala-San Nicolas, Maria |
author_sort | Martin-Orozco, Elena |
collection | PubMed |
description | WNT/β-catenin signaling is involved in many physiological processes. Its implication in embryonic development, cell migration, and polarization has been shown. Nevertheless, alterations in this signaling have also been related with pathological events such as sustaining and proliferating the cancer stem cell (CSC) subset present in the tumor bulk. Related with this, WNT signaling has been associated with the maintenance, expansion, and epithelial-mesenchymal transition of stem cells, and furthermore with two distinctive features of this tumor population: therapeutic resistance (MDR, multidrug resistance) and immune escape. These mechanisms are developed and maintained by WNT activation through the transcriptional control of the genes involved in such processes. This review focuses on the description of the best known WNT pathways and the molecules involved in them. Special attention is given to the WNT cascade proteins deregulated in tumors, which have a decisive role in tumor survival. Some of these proteins function as extrusion pumps that, in the course of chemotherapy, expel the drugs from the cells; others help the tumoral cells hide from the immune effector mechanisms. Among the WNT targets involved in drug resistance, the drug extrusion pump MDR-1 (P-GP, ABCB1) and the cell adhesion molecules from the CD44 family are highlighted. The chemokine CCL4 and the immune checkpoint proteins CD47 and PD-L1 are included in the list of WNT target molecules with a role in immunity escape. This pathway should be a main target in cancer therapy as WNT signaling activation is essential for tumor progression and survival, even in the presence of the anti-tumoral immune response and/or antineoplastic drugs. The appropriate design and combination of anti-tumoral strategies, based on the modulation of WNT mediators and/or protein targets, could negatively affect the growth of tumoral cells, improving the efficacy of these types of therapies. |
format | Online Article Text |
id | pubmed-6934036 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-69340362020-01-09 WNT Signaling in Tumors: The Way to Evade Drugs and Immunity Martin-Orozco, Elena Sanchez-Fernandez, Ana Ortiz-Parra, Irene Ayala-San Nicolas, Maria Front Immunol Immunology WNT/β-catenin signaling is involved in many physiological processes. Its implication in embryonic development, cell migration, and polarization has been shown. Nevertheless, alterations in this signaling have also been related with pathological events such as sustaining and proliferating the cancer stem cell (CSC) subset present in the tumor bulk. Related with this, WNT signaling has been associated with the maintenance, expansion, and epithelial-mesenchymal transition of stem cells, and furthermore with two distinctive features of this tumor population: therapeutic resistance (MDR, multidrug resistance) and immune escape. These mechanisms are developed and maintained by WNT activation through the transcriptional control of the genes involved in such processes. This review focuses on the description of the best known WNT pathways and the molecules involved in them. Special attention is given to the WNT cascade proteins deregulated in tumors, which have a decisive role in tumor survival. Some of these proteins function as extrusion pumps that, in the course of chemotherapy, expel the drugs from the cells; others help the tumoral cells hide from the immune effector mechanisms. Among the WNT targets involved in drug resistance, the drug extrusion pump MDR-1 (P-GP, ABCB1) and the cell adhesion molecules from the CD44 family are highlighted. The chemokine CCL4 and the immune checkpoint proteins CD47 and PD-L1 are included in the list of WNT target molecules with a role in immunity escape. This pathway should be a main target in cancer therapy as WNT signaling activation is essential for tumor progression and survival, even in the presence of the anti-tumoral immune response and/or antineoplastic drugs. The appropriate design and combination of anti-tumoral strategies, based on the modulation of WNT mediators and/or protein targets, could negatively affect the growth of tumoral cells, improving the efficacy of these types of therapies. Frontiers Media S.A. 2019-12-20 /pmc/articles/PMC6934036/ /pubmed/31921125 http://dx.doi.org/10.3389/fimmu.2019.02854 Text en Copyright © 2019 Martin-Orozco, Sanchez-Fernandez, Ortiz-Parra and Ayala-San Nicolas. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Martin-Orozco, Elena Sanchez-Fernandez, Ana Ortiz-Parra, Irene Ayala-San Nicolas, Maria WNT Signaling in Tumors: The Way to Evade Drugs and Immunity |
title | WNT Signaling in Tumors: The Way to Evade Drugs and Immunity |
title_full | WNT Signaling in Tumors: The Way to Evade Drugs and Immunity |
title_fullStr | WNT Signaling in Tumors: The Way to Evade Drugs and Immunity |
title_full_unstemmed | WNT Signaling in Tumors: The Way to Evade Drugs and Immunity |
title_short | WNT Signaling in Tumors: The Way to Evade Drugs and Immunity |
title_sort | wnt signaling in tumors: the way to evade drugs and immunity |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934036/ https://www.ncbi.nlm.nih.gov/pubmed/31921125 http://dx.doi.org/10.3389/fimmu.2019.02854 |
work_keys_str_mv | AT martinorozcoelena wntsignalingintumorsthewaytoevadedrugsandimmunity AT sanchezfernandezana wntsignalingintumorsthewaytoevadedrugsandimmunity AT ortizparrairene wntsignalingintumorsthewaytoevadedrugsandimmunity AT ayalasannicolasmaria wntsignalingintumorsthewaytoevadedrugsandimmunity |