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New Insights on the Nuclear Functions and Targeting of FAK in Cancer

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase over-expressed and activated in both adult and pediatric cancers, where it plays important roles in the regulation of pathogenesis and progression of the malignant phenotype. FAK exerts its functions in cancer by two different ways: a kin...

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Autores principales: Pomella, Silvia, Cassandri, Matteo, Braghini, Maria Rita, Marampon, Francesco, Alisi, Anna, Rota, Rossella
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8874710/
https://www.ncbi.nlm.nih.gov/pubmed/35216114
http://dx.doi.org/10.3390/ijms23041998
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author Pomella, Silvia
Cassandri, Matteo
Braghini, Maria Rita
Marampon, Francesco
Alisi, Anna
Rota, Rossella
author_facet Pomella, Silvia
Cassandri, Matteo
Braghini, Maria Rita
Marampon, Francesco
Alisi, Anna
Rota, Rossella
author_sort Pomella, Silvia
collection PubMed
description Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase over-expressed and activated in both adult and pediatric cancers, where it plays important roles in the regulation of pathogenesis and progression of the malignant phenotype. FAK exerts its functions in cancer by two different ways: a kinase activity in the cytoplasm, mainly dependent on the integrin signaling, and a scaffolding activity into the nucleus by networking with different gene expression regulators. For this reason, FAK has to be considered a target with high therapeutic values. Indeed, evidence suggests that FAK targeting could be effective, either alone or in combination, with other already available treatments. Here, we propose an overview of the novel insights about FAK’s structure and nuclear functions, with a special focus on the recent findings concerning the roles of this protein in cancer. Additionally, we provide a recent update on FAK inhibitors that are currently in clinical trials for patients with cancer, and discuss the challenge and future directions of drug-based anti-FAK targeted therapies.
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spelling pubmed-88747102022-02-26 New Insights on the Nuclear Functions and Targeting of FAK in Cancer Pomella, Silvia Cassandri, Matteo Braghini, Maria Rita Marampon, Francesco Alisi, Anna Rota, Rossella Int J Mol Sci Review Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase over-expressed and activated in both adult and pediatric cancers, where it plays important roles in the regulation of pathogenesis and progression of the malignant phenotype. FAK exerts its functions in cancer by two different ways: a kinase activity in the cytoplasm, mainly dependent on the integrin signaling, and a scaffolding activity into the nucleus by networking with different gene expression regulators. For this reason, FAK has to be considered a target with high therapeutic values. Indeed, evidence suggests that FAK targeting could be effective, either alone or in combination, with other already available treatments. Here, we propose an overview of the novel insights about FAK’s structure and nuclear functions, with a special focus on the recent findings concerning the roles of this protein in cancer. Additionally, we provide a recent update on FAK inhibitors that are currently in clinical trials for patients with cancer, and discuss the challenge and future directions of drug-based anti-FAK targeted therapies. MDPI 2022-02-11 /pmc/articles/PMC8874710/ /pubmed/35216114 http://dx.doi.org/10.3390/ijms23041998 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
Pomella, Silvia
Cassandri, Matteo
Braghini, Maria Rita
Marampon, Francesco
Alisi, Anna
Rota, Rossella
New Insights on the Nuclear Functions and Targeting of FAK in Cancer
title New Insights on the Nuclear Functions and Targeting of FAK in Cancer
title_full New Insights on the Nuclear Functions and Targeting of FAK in Cancer
title_fullStr New Insights on the Nuclear Functions and Targeting of FAK in Cancer
title_full_unstemmed New Insights on the Nuclear Functions and Targeting of FAK in Cancer
title_short New Insights on the Nuclear Functions and Targeting of FAK in Cancer
title_sort new insights on the nuclear functions and targeting of fak in cancer
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8874710/
https://www.ncbi.nlm.nih.gov/pubmed/35216114
http://dx.doi.org/10.3390/ijms23041998
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