Role of p-21-activated kinases in cancer progression

Int Rev Cell Mol Biol. 2014:309:347-87. doi: 10.1016/B978-0-12-800255-1.00007-7.

Abstract

The p-21-activated kinases (PAKs) are downstream effectors of Rho GTPases Rac and Cdc42. The PAK family consists of six members which are segregated into two subgroups (Group I and Group II) based on sequence homology. Group I PAKs (PAK1-3) are the most extensively studied but there is increasing interest in the functionality of Group II PAKs (PAK4-6). The PAK family proteins are thought to play an important role in many different cellular processes, some of which have particular significance in the context of cancer progression. This review explores established and more recent data, linking the PAK family kinases to cancer progression including expression profiles, evasion of apoptosis, promotion of cell survival, and regulation of cell invasion. Finally, we discuss attempts to therapeutically target the PAK family and outline the major obstacles that still need to be overcome.

Keywords: Actin cytoskeleton; Apoptosis; Cell invasion; Cell survival; LIM kinase; Metastasis; p-21-activated kinase.

Publication types

  • Review

MeSH terms

  • Animals
  • Disease Progression*
  • Humans
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy
  • Neoplasms / enzymology*
  • Neoplasms / pathology*
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • p21-Activated Kinases / antagonists & inhibitors
  • p21-Activated Kinases / chemistry
  • p21-Activated Kinases / metabolism*

Substances

  • Protein Kinase Inhibitors
  • p21-Activated Kinases