Abstract
AKT (or protein kinase B) and focal adhesion kinase (FAK) are two important kinases that regulate various cellular functions. Each is overexpressed and/or aberrantly activated in diverse cancers. Several small molecular inhibitors targeting either AKT or FAK are in development or in clinical trials. It is well established that FAK is an upstream regulator of AKT signaling pathway in various cancer cell lines and in xenograft tumor models. However, very recent reports from our laboratory and others demonstrate that AKT can also directly regulate FAK through direct association and serine phosphorylation. This indicates that AKT and FAK may be dual therapeutic targets for pharmacologic intervention in the treatment of primary and metastatic cancer. FAK-AKT interaction is particularly critical for metastatic adhesion. We review recent developments in AKT and FAK signaling in cancer with the particular emphasis on the novel signaling pathways in which FAK is downstream of AKT. We also provide an update on inhibitors targeting AKT or FAK currently in clinical trials.
Keywords: AKT, AKT1, AKT2, cancer, cancer metastasis, cell signaling, differentiation, FAK, FERM, invasion, isoform, migration, proliferation, Src
Anti-Cancer Agents in Medicinal Chemistry
Title: Protein Kinase B/AKT and Focal Adhesion Kinase: Two Close Signaling Partners in Cancer
Volume: 11 Issue: 10
Author(s): Shouye Wang and Marc D. Basson
Affiliation:
Keywords: AKT, AKT1, AKT2, cancer, cancer metastasis, cell signaling, differentiation, FAK, FERM, invasion, isoform, migration, proliferation, Src
Abstract: AKT (or protein kinase B) and focal adhesion kinase (FAK) are two important kinases that regulate various cellular functions. Each is overexpressed and/or aberrantly activated in diverse cancers. Several small molecular inhibitors targeting either AKT or FAK are in development or in clinical trials. It is well established that FAK is an upstream regulator of AKT signaling pathway in various cancer cell lines and in xenograft tumor models. However, very recent reports from our laboratory and others demonstrate that AKT can also directly regulate FAK through direct association and serine phosphorylation. This indicates that AKT and FAK may be dual therapeutic targets for pharmacologic intervention in the treatment of primary and metastatic cancer. FAK-AKT interaction is particularly critical for metastatic adhesion. We review recent developments in AKT and FAK signaling in cancer with the particular emphasis on the novel signaling pathways in which FAK is downstream of AKT. We also provide an update on inhibitors targeting AKT or FAK currently in clinical trials.
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Cite this article as:
Wang Shouye and D. Basson Marc, Protein Kinase B/AKT and Focal Adhesion Kinase: Two Close Signaling Partners in Cancer, Anti-Cancer Agents in Medicinal Chemistry 2011; 11 (10) . https://dx.doi.org/10.2174/187152011797927661
DOI https://dx.doi.org/10.2174/187152011797927661 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
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