Publication: Wnt signaling in tumors: The way to evade drugs and immunity
Authors
Sánchez-Fernández, Ana ; Ortíz-Parra, Irene ; Ayala-San Nicolás, María ; Martín-Orozco Santiago, María Elena
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Publisher
Frontiers in Immunology
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DOI
doi: 10.3389/fimmu.2019.02854
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info:eu-repo/semantics/article
Description
©2019. This manuscript version is made available under the CC-BY 4.0 license http://creativecommons.org/licenses/by /4.0/
This document is the Published, version of a Published Work that appeared in final form in Frontiers in Immunology. To access the final edited and published work see doi: 10.3389/fimmu.2019.02854
Abstract
WNT/b-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 amain 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.
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Citation
Frontiers in Immunology
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