Tracing PAKs from GI inflammation to cancer

Gut. 2014 Jul;63(7):1173-84. doi: 10.1136/gutjnl-2014-306768. Epub 2014 May 7.

Abstract

P-21 activated kinases (PAKs) are effectors of Rac1/Cdc42 which coordinate signals from the cell membrane to the nucleus. Activation of PAKs drive important signalling pathways including mitogen activated protein kinase, phospoinositide 3-kinase (PI3K/AKT), NF-κB and Wnt/β-catenin. Intestinal PAK1 expression increases with inflammation and malignant transformation, although the biological relevance of PAKs in the development and progression of GI disease is only incompletely understood. This review highlights the importance of altered PAK activation within GI inflammation, emphasises its effect on oncogenic signalling and discusses PAKs as therapeutic targets of chemoprevention.

Keywords: COLON CARCINOGENESIS; GASTROINTESTINAL CANCER; INFLAMMATORY BOWEL DISEASE.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Cell Transformation, Neoplastic*
  • Disease Progression
  • Gastrointestinal Neoplasms / enzymology*
  • Gastrointestinal Neoplasms / pathology
  • Humans
  • Inflammation / enzymology*
  • Inflammation / pathology
  • Signal Transduction
  • p21-Activated Kinases / metabolism*

Substances

  • Biomarkers, Tumor
  • PAK1 protein, human
  • p21-Activated Kinases