The Pak4 Protein Kinase Plays a Key Role in Cell Survival and Tumorigenesis in Athymic Mice
Open Access
- 1 July 2008
- journal article
- Published by American Association for Cancer Research (AACR) in Molecular Cancer Research
- Vol. 6 (7), 1215-1224
- https://doi.org/10.1158/1541-7786.mcr-08-0087
Abstract
Pak4 is a member of the B group of p21-activated (Pak) kinases, originally identified as an effector protein for Cdc42. Although Pak4 is expressed at low levels in most adult tissues, it is highly overexpressed in tumor cell lines. Here, we show that Pak4 is also overexpressed in primary tumors, including colon, esophageal, and mammary tumors. Overexpression of Pak4 also leads to tumor formation in athymic mice, whereas deletion of Pak4 inhibits tumorigenesis. Although a constitutively active Pak4 mutant was previously shown to promote oncogenic transformation in cultured cells, our results are the first to show that Pak4 also promotes tumorigenesis in experimental animals. Furthermore, these results show for the first time that not only constitutively active Pak4, but also wild-type Pak4, is transforming, when experimental animals are used. These results are highly significant because wild-type Pak4, rather than activated Pak4, is overexpressed in tumor cells. Our results suggest that overexpression or activation of Pak4 is a key step in oncogenic transformation, due to its ability to promote cell survival and subsequent uncontrolled proliferation. The finding that Pak4 is up-regulated in so many types of cancers indicates that Pak4 may play a vital role in a wide range of different types of cancer. This makes it an attractive candidate for drug therapy for different types of cancer. (Mol Cancer Res 2008;6(7):1215–24)Keywords
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This publication has 25 references indexed in Scilit:
- Production of adenoviral vectors and its recoveryProcess Biochemistry, 2007
- Apoptosis: a basic biological phenomenon with wide‐ranging implications in human diseaseJournal of Internal Medicine, 2005
- Death Receptor-Induced Activation of Initiator Caspase 8 Is Antagonized by Serine/Threonine Kinase PAK4Molecular and Cellular Biology, 2003
- PAK4 Kinase Is Essential for Embryonic Viability and for Proper Neuronal DevelopmentMolecular and Cellular Biology, 2003
- Conditional Knock-out of Integrin-linked Kinase Demonstrates an Essential Role in Protein Kinase B/Akt ActivationJournal of Biological Chemistry, 2003
- Requirement for PAK4 in the Anchorage-independent Growth of Human Cancer Cell LinesJournal of Biological Chemistry, 2002
- Activated PAK4 Regulates Cell Adhesion and Anchorage-Independent GrowthMolecular and Cellular Biology, 2001
- Biochemical Pathways of Caspase Activation During ApoptosisAnnual Review of Cell and Developmental Biology, 1999
- p21-Activated protein kinase: a crucial component of morphological signaling?Trends in Biochemical Sciences, 1999
- Emerging from the Pak: the p21-activated protein kinase familyTrends in Cell Biology, 1997