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.
Bibliographical noteFunding 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: 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).
© 2018 by the authors. Licensee MDPI, Basel, Switzerland.
ASJC Scopus subject areas
- Cancer Research