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The Crosstalk between FAK and Wnt Signaling Pathways in Cancer and Its Therapeutic Implication

Focal adhesion kinase (FAK) and Wnt signaling pathways are important contributors to tumorigenesis in several cancers. While most results come from studies investigating these pathways individually, there is increasing evidence of a functional crosstalk between both signaling pathways during develop...

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Autores principales: Wörthmüller, Janine, Rüegg, Curzio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730291/
https://www.ncbi.nlm.nih.gov/pubmed/33266025
http://dx.doi.org/10.3390/ijms21239107
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author Wörthmüller, Janine
Rüegg, Curzio
author_facet Wörthmüller, Janine
Rüegg, Curzio
author_sort Wörthmüller, Janine
collection PubMed
description Focal adhesion kinase (FAK) and Wnt signaling pathways are important contributors to tumorigenesis in several cancers. While most results come from studies investigating these pathways individually, there is increasing evidence of a functional crosstalk between both signaling pathways during development and tumor progression. A number of FAK–Wnt interactions are described, suggesting an intricate, context-specific, and cell type-dependent relationship. During development for instance, FAK acts mainly upstream of Wnt signaling; and although in intestinal homeostasis and mucosal regeneration Wnt seems to function upstream of FAK signaling, FAK activates the Wnt/β-catenin signaling pathway during APC-driven intestinal tumorigenesis. In breast, lung, and pancreatic cancers, FAK is reported to modulate the Wnt signaling pathway, while in prostate cancer, FAK is downstream of Wnt. In malignant mesothelioma, FAK and Wnt show an antagonistic relationship: Inhibiting FAK signaling activates the Wnt pathway and vice versa. As the identification of effective Wnt inhibitors to translate in the clinical setting remains an outstanding challenge, further understanding of the functional interaction between Wnt and FAK could reveal new therapeutic opportunities and approaches greatly needed in clinical oncology. In this review, we summarize some of the most relevant interactions between FAK and Wnt in different cancers, address the current landscape of Wnt- and FAK-targeted therapies in different clinical trials, and discuss the rationale for targeting the FAK–Wnt crosstalk, along with the possible translational implications.
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spelling pubmed-77302912020-12-12 The Crosstalk between FAK and Wnt Signaling Pathways in Cancer and Its Therapeutic Implication Wörthmüller, Janine Rüegg, Curzio Int J Mol Sci Review Focal adhesion kinase (FAK) and Wnt signaling pathways are important contributors to tumorigenesis in several cancers. While most results come from studies investigating these pathways individually, there is increasing evidence of a functional crosstalk between both signaling pathways during development and tumor progression. A number of FAK–Wnt interactions are described, suggesting an intricate, context-specific, and cell type-dependent relationship. During development for instance, FAK acts mainly upstream of Wnt signaling; and although in intestinal homeostasis and mucosal regeneration Wnt seems to function upstream of FAK signaling, FAK activates the Wnt/β-catenin signaling pathway during APC-driven intestinal tumorigenesis. In breast, lung, and pancreatic cancers, FAK is reported to modulate the Wnt signaling pathway, while in prostate cancer, FAK is downstream of Wnt. In malignant mesothelioma, FAK and Wnt show an antagonistic relationship: Inhibiting FAK signaling activates the Wnt pathway and vice versa. As the identification of effective Wnt inhibitors to translate in the clinical setting remains an outstanding challenge, further understanding of the functional interaction between Wnt and FAK could reveal new therapeutic opportunities and approaches greatly needed in clinical oncology. In this review, we summarize some of the most relevant interactions between FAK and Wnt in different cancers, address the current landscape of Wnt- and FAK-targeted therapies in different clinical trials, and discuss the rationale for targeting the FAK–Wnt crosstalk, along with the possible translational implications. MDPI 2020-11-30 /pmc/articles/PMC7730291/ /pubmed/33266025 http://dx.doi.org/10.3390/ijms21239107 Text en © 2020 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Wörthmüller, Janine
Rüegg, Curzio
The Crosstalk between FAK and Wnt Signaling Pathways in Cancer and Its Therapeutic Implication
title The Crosstalk between FAK and Wnt Signaling Pathways in Cancer and Its Therapeutic Implication
title_full The Crosstalk between FAK and Wnt Signaling Pathways in Cancer and Its Therapeutic Implication
title_fullStr The Crosstalk between FAK and Wnt Signaling Pathways in Cancer and Its Therapeutic Implication
title_full_unstemmed The Crosstalk between FAK and Wnt Signaling Pathways in Cancer and Its Therapeutic Implication
title_short The Crosstalk between FAK and Wnt Signaling Pathways in Cancer and Its Therapeutic Implication
title_sort crosstalk between fak and wnt signaling pathways in cancer and its therapeutic implication
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730291/
https://www.ncbi.nlm.nih.gov/pubmed/33266025
http://dx.doi.org/10.3390/ijms21239107
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