Review
p21-activated kinases and gastrointestinal cancer

https://doi.org/10.1016/j.bbamcr.2012.10.015Get rights and content
Under an Elsevier user license
open archive

Abstract

p21-activated kinases (PAKs) were initially identified as effector proteins downstream from GTPases of the Rho family. To date, six members of the PAK family have been discovered in mammalian cells. PAKs play important roles in growth factor signalling, cytoskeletal remodelling, gene transcription, cell proliferation and oncogenic transformation. A large body of research has demonstrated that PAKs are up-regulated in several human cancers, and that their overexpression is linked to tumour progression and resistance to therapy. Structural and biochemical studies have revealed the mechanisms involved in PAK signalling, and opened the way to the development of PAK-targeted therapies for cancer treatment. Here we summarise recent findings from biological and clinical research on the role of PAKs in gastrointestinal cancer, and discuss the current status of PAK-targeted anticancer therapies.

Highlights

► The p21-activated kinases (PAKs) are up-regulated in several human cancers. ► PAK overexpression is linked to tumour progression and resistance to therapy. ► PAK1 connects multiple signalling pathways important in colorectal cancer. ► PAKs are attractive targets for new therapies for gastrointestinal cancers.

Abbreviations

AID
auto-inhibitory domain
CDK5RAP3
CDK5 kinase regulatory subunit-associated protein 3
CRC
colorectal carcinoma
EGFR
epithelial growth factor receptor
GAP
GTPase-activating protein
HBV
hepatitis B virus
HBx
HBV X protein
HCC
hepatocellular carcinoma
PAK
p21-activated kinase
PBD
p21-binding domain
PSD
pseudosubstrate domain

Keywords

PAK
Signalling
Liver cancer
Pancreatic cancer
Gastric cancer
Colorectal cancer

Cited by (0)