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Endogenous Control Mechanisms of FAK and PYK2 and Their Relevance to Cancer Development
Focal adhesion kinase (FAK) and its close paralogue, proline-rich tyrosine kinase 2 (PYK2), are key regulators of aggressive spreading and metastasis of cancer cells. While targeted small-molecule inhibitors of FAK and PYK2 have been found to have promising antitumor activity, their clinical long-te...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6025627/ https://www.ncbi.nlm.nih.gov/pubmed/29891810 http://dx.doi.org/10.3390/cancers10060196 |
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author | Naser, Rayan Aldehaiman, Abdullah Díaz-Galicia, Escarlet Arold, Stefan T. |
author_facet | Naser, Rayan Aldehaiman, Abdullah Díaz-Galicia, Escarlet Arold, Stefan T. |
author_sort | Naser, Rayan |
collection | PubMed |
description | Focal adhesion kinase (FAK) and its close paralogue, proline-rich tyrosine kinase 2 (PYK2), are key regulators of aggressive spreading and metastasis of cancer cells. While targeted small-molecule inhibitors of FAK and PYK2 have been found to have promising antitumor activity, their clinical long-term efficacy may be undermined by the strong capacity of cancer cells to evade anti-kinase drugs. In healthy cells, the expression and/or function of FAK and PYK2 is tightly controlled via modulation of gene expression, competing alternatively spliced forms, non-coding RNAs, and proteins that directly or indirectly affect kinase activation or protein stability. The molecular factors involved in this control are frequently deregulated in cancer cells. Here, we review the endogenous mechanisms controlling FAK and PYK2, and with particular focus on how these mechanisms could inspire or improve anticancer therapies. |
format | Online Article Text |
id | pubmed-6025627 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-60256272018-07-09 Endogenous Control Mechanisms of FAK and PYK2 and Their Relevance to Cancer Development Naser, Rayan Aldehaiman, Abdullah Díaz-Galicia, Escarlet Arold, Stefan T. Cancers (Basel) Review Focal adhesion kinase (FAK) and its close paralogue, proline-rich tyrosine kinase 2 (PYK2), are key regulators of aggressive spreading and metastasis of cancer cells. While targeted small-molecule inhibitors of FAK and PYK2 have been found to have promising antitumor activity, their clinical long-term efficacy may be undermined by the strong capacity of cancer cells to evade anti-kinase drugs. In healthy cells, the expression and/or function of FAK and PYK2 is tightly controlled via modulation of gene expression, competing alternatively spliced forms, non-coding RNAs, and proteins that directly or indirectly affect kinase activation or protein stability. The molecular factors involved in this control are frequently deregulated in cancer cells. Here, we review the endogenous mechanisms controlling FAK and PYK2, and with particular focus on how these mechanisms could inspire or improve anticancer therapies. MDPI 2018-06-11 /pmc/articles/PMC6025627/ /pubmed/29891810 http://dx.doi.org/10.3390/cancers10060196 Text en © 2018 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 Naser, Rayan Aldehaiman, Abdullah Díaz-Galicia, Escarlet Arold, Stefan T. Endogenous Control Mechanisms of FAK and PYK2 and Their Relevance to Cancer Development |
title | Endogenous Control Mechanisms of FAK and PYK2 and Their Relevance to Cancer Development |
title_full | Endogenous Control Mechanisms of FAK and PYK2 and Their Relevance to Cancer Development |
title_fullStr | Endogenous Control Mechanisms of FAK and PYK2 and Their Relevance to Cancer Development |
title_full_unstemmed | Endogenous Control Mechanisms of FAK and PYK2 and Their Relevance to Cancer Development |
title_short | Endogenous Control Mechanisms of FAK and PYK2 and Their Relevance to Cancer Development |
title_sort | endogenous control mechanisms of fak and pyk2 and their relevance to cancer development |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6025627/ https://www.ncbi.nlm.nih.gov/pubmed/29891810 http://dx.doi.org/10.3390/cancers10060196 |
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