Jeyanthy , Eswaran and Da-Qiang, Li and Anil , Shah and Rakesh, Kuma (2012) Molecular Pathways: Targeting P21-Activated Kinase 1 Signaling in Cancer—Opportunities, Challenges, and Limitations. Clinical cancer research : an official journal of the American Association for Cancer Research., 18(14). 3743-3749. . ISSN 1078-0432

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Abstract

The evolution of cancer cells involves deregulation of highly regulated fundamental pathways that are central to normal cellular architecture and functions. p21-activated kinase 1 (PAK1) was initially identified as a downstream effector of the GTPases Rac and Cdc42. Subsequent studies uncovered a variety of new functions for this kinase in growth factor and steroid receptor signaling, cytoskeleton remodeling, cell survival, oncogenic transformation, and gene transcription, largely through systematic discovery of its direct, physiologically relevant substrates. PAK1 is widely upregulated in several human cancers, such as hormone-dependent cancer, and is intimately linked to tumor progression and therapeutic resistance. These exciting developments combined with the kinase-independent role of PAK1-centered phenotypic signaling in cancer cells elevated PAK1 as an attractive drug target. Structural and biochemical studies revealed the precise mechanism of PAK1 activation, offering the possibility to develop PAK1-targeted cancer therapeutic approaches. In addition, emerging reports suggest the potential of PAK1 and its specific phosphorylated substrates as cancer prognostic markers. Here, we summarize recent findings about the PAK1 molecular pathways in human cancer and discuss the current status of PAK1-targeted anticancer therapies. Clin Cancer Res; 18(14); 3743–9. �2012 AACR

Item Type:	Article
Uncontrolled Keywords:	PAK1, Growth factor signaling, Cytoskeleton, Oncogenic transformation, Chromatin and nuclear signaling, Protein kinase inhibitor
Subjects:	Cancer Research
Depositing User:	Central Library RGCB
Date Deposited:	22 Dec 2016 03:19
Last Modified:	22 Dec 2016 05:48
URI:	http://rgcb.sciencecentral.in/id/eprint/45

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