Regulation of E-cadherin expression and beta-catenin/Tcf transcriptional activity by the integrin-linked kinase

Biochim Biophys Acta. 2004 Apr 1;1691(1):1-15. doi: 10.1016/j.bbamcr.2003.12.002.

Abstract

Integrin-linked kinase (ILK) is a serine/threonine protein kinase which interacts with the cytoplasmic domains of beta1 and beta3 integrins. ILK structure and its localization at the focal adhesion allows it not only to interact with different structural proteins, but also to mediate many different signalling pathways. Extracellular matrices (ECM) and growth factors each stimulate ILK signalling. Constitutive activation of ILK in epithelial cells results in oncogenic phenotypes such as disruption of cell extracellular matrix and cell to cell interactions, suppression of suspension-induced apoptosis, and induction of anchorage independent cell growth and cell cycle progression. More specifically, pathological overexpression of ILK results in down-regulation of E-cadherin expression, and nuclear accumulation of beta-catenin, leading to the subsequent activation of the beta-catenin/Tcf transcription complex, the downstream components of the Wnt signalling pathway. Here we review the data implicating ILK in the regulation of these two signalling pathways, and discuss recent novel insights into the molecular basis and requirement of ILK in the process of epithelial to mesenchymal transformation (EMT).

Publication types

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

MeSH terms

  • Animals
  • Cadherins / biosynthesis
  • Cadherins / genetics*
  • Cytoskeletal Proteins / genetics*
  • Cytoskeletal Proteins / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation, Developmental
  • Humans
  • Lymphoid Enhancer-Binding Factor 1
  • Protein Serine-Threonine Kinases / physiology*
  • Signal Transduction
  • Trans-Activators / genetics*
  • Trans-Activators / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • beta Catenin

Substances

  • CTNNB1 protein, human
  • Cadherins
  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • Lymphoid Enhancer-Binding Factor 1
  • Trans-Activators
  • Transcription Factors
  • beta Catenin
  • integrin-linked kinase
  • Protein Serine-Threonine Kinases