Regulation of E-cadherin expression and beta-catenin/Tcf transcriptional activity by the integrin-linked kinase.
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).
Oloumi
Arusha
A
British Columbia Cancer Agency and Jack Bell Research Centre, University of British Columbia, Vancouver Hospital, 2660 Oak St. Vancouver, BC, Canada V6H 3Z6.
McPhee
Timothy
T
Dedhar
Shoukat
S
D000818:Animals; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051821:Lymphoid Enhancer-Binding Factor 1; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D051176:beta Catenin; D000099200:Scaffold Protein ILK
D015820:Cadherins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D051821:Lymphoid Enhancer-Binding Factor 1; D017346:Protein Serine-Threonine Kinases; D015534:Trans-Activators; D014157:Transcription Factors; D051176:beta Catenin; D000099200:Scaffold Protein ILK; C495270:CTNNB1 protein, human