Abstract
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.
Highlights
Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase with a molecular weight of 125 kDa that contributes to the regulation of different cellular processes, including cell survival, proliferation, apoptosis, adhesion, migration and mechano-transduction
FAK was described for the first time in 1992 by Schaller et al as a central protein associated to the sub-cellular structures named focal adhesions (FAs), which regulate signaling events in response to the extracellular matrix (ECM) [3]
FAK signaling represents a convergence node of key cellular processes regulated by integrins and growth factor receptors to drive numerous cell functions
Summary
Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase with a molecular weight of 125 kDa that contributes to the regulation of different cellular processes, including cell survival, proliferation, apoptosis, adhesion, migration and mechano-transduction (ref. [1] and reviewed in [2]). Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase with a molecular weight of 125 kDa that contributes to the regulation of different cellular processes, including cell survival, proliferation, apoptosis, adhesion, migration and mechano-transduction FAK was described for the first time in 1992 by Schaller et al as a central protein associated to the sub-cellular structures named focal adhesions (FAs), which regulate signaling events in response to the extracellular matrix (ECM) [3]. Over the last ten years, in addition to this kinase-dependent function, an unexpected kinase-independent role in the scaffolding and regulation of gene transcription was discovered for FAK We summarize the current knowledge on FAK structure and the novel insights into its scaffolding nuclear functions, mainly focusing on recent updates of its role in cancer. We give an overview of FAK inhibitors currently in clinical trials on patients with cancer and discuss the challenge and future directions of drug-based anti-FAK targeted therapies
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