Endogenous control mechanisms of FAK and PYK2 and their relevance to cancer development

Rayan Naser; Abdullah Aldehaiman; Escarlet Díaz-Galicia; Stefan T. Arold

doi:10.3390/cancers10060196

Endogenous control mechanisms of FAK and PYK2 and their relevance to cancer development

Rayan Naser, Abdullah Aldehaiman, Escarlet Díaz-Galicia, Stefan T. Arold^*

^*Corresponding author for this work

Research output: Contribution to journal › Review article › peer-review

36 Scopus citations

Abstract

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.

Original language	English (US)
Article number	196
Journal	Cancers
Volume	10
Issue number	6
DOIs	https://doi.org/10.3390/cancers10060196
State	Published - Jun 11 2018

Bibliographical note

Funding Information:
This publication was supported by King Abdullah University of Science and Technology (KAUST) through baseline funds and Award No. URF/1/2602-01-01 from the Office of Sponsored Research (OSR). We thank Virginia Unkefer for editorial assistance and Jean-Antoine Girault, Seungbeom Hong, Bilal M. Qureshi and Afaque-Ahmad Momin for suggestions and discussions. We apologize to all colleagues whose research could not be discussed because of space constraints.

Funding Information:
Funding: This publication was supported by King Abdullah University of Science and Technology (KAUST) through baseline funds and Award No. URF/1/2602-01-01 from the Office of Sponsored Research (OSR).

Publisher Copyright:
© 2018 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

Anoikis
Chaperon
Dimerization
FIP200
LKB1
MiRNA
Motility
PI3K
PTEN
Regulation

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/cancers10060196

Cite this

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abstract = "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.",

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note = "Funding Information: This publication was supported by King Abdullah University of Science and Technology (KAUST) through baseline funds and Award No. URF/1/2602-01-01 from the Office of Sponsored Research (OSR). We thank Virginia Unkefer for editorial assistance and Jean-Antoine Girault, Seungbeom Hong, Bilal M. Qureshi and Afaque-Ahmad Momin for suggestions and discussions. We apologize to all colleagues whose research could not be discussed because of space constraints. Funding Information: Funding: This publication was supported by King Abdullah University of Science and Technology (KAUST) through baseline funds and Award No. URF/1/2602-01-01 from the Office of Sponsored Research (OSR). Publisher Copyright: {\textcopyright} 2018 by the authors. Licensee MDPI, Basel, Switzerland.",

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N1 - Funding Information: This publication was supported by King Abdullah University of Science and Technology (KAUST) through baseline funds and Award No. URF/1/2602-01-01 from the Office of Sponsored Research (OSR). We thank Virginia Unkefer for editorial assistance and Jean-Antoine Girault, Seungbeom Hong, Bilal M. Qureshi and Afaque-Ahmad Momin for suggestions and discussions. We apologize to all colleagues whose research could not be discussed because of space constraints. Funding Information: Funding: This publication was supported by King Abdullah University of Science and Technology (KAUST) through baseline funds and Award No. URF/1/2602-01-01 from the Office of Sponsored Research (OSR). Publisher Copyright: © 2018 by the authors. Licensee MDPI, Basel, Switzerland.

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N2 - 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.

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KW - Regulation

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Endogenous control mechanisms of FAK and PYK2 and their relevance to cancer development

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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