[Frontiers in Bioscience 16, 849-864, January 1, 2011]

Signalling to cancer cell invasion through PAK family kinases

Andrew Whale1, Fariesha Nur Hashim2, Sally Fram2, Gareth E. Jones1, Claire M. Wells2

1Randall Division of Cell and Molecular Biophysics, King's College London, 2Division of Cancer Studies, King's College London

TABLE OF CONTENTS

1. Abstract
2. Introduction
2.1. Cancer cell invasion
2.2. PAK family kinases
2.2.1. Domain structure
2.2.2. Expression and localisation
2.2.3. Mouse knockout studies
3. Group I PAKs
3.1. Group I PAKs and cancer
3.2. Group I PAKs - Upstream regulators
3.3. Group I PAKs signalling to the cytoskeleton
3.4. Group I PAKs and cancer cell invasion
4. Group II PAKs
4.1. Group II PAKs and cancer
4.2. Group II PAKs - Upstream regulators
4.3. Group II signalling to the cytoskeleton
4.4.Group II PAKs and cancer cell invasion
5. Perspectives
6. References

1. ABSTRACT

Cancer cell metastasis involves a series of changes in cell behaviour, driven by oncogenic transformation, that leads to local tissue invasion, migration through extracellular matrix, entry into the vascular or lymphatic system and colonisation of distant sites. It is well established that the Rho family GTPases Rho, Rac and Cdc42 orchestrate many of the processes required during metastasis. The Rho family GTPases regulate cellular behaviour through their interaction with downstream effector proteins. The p-21 activated kinases (PAKs), effector proteins for Rac and Cdc42, are known to be important regulators of cell migration and invasion. There are six mammalian PAKs which can be divided into two groups: group I PAKs (PAK1-3) and group II PAKs (PAK4-6). Although the two PAK groups are architecturally similar there are differences in their mode of regulation suggesting their cellular functions are likely to be different. This review will focus on the latest evidence relating to the role of PAK family kinases in the cell signalling pathways that drive cancer cell migration and invasion.