Drs. McDonald and Oloumi contributed equally to the manuscript.
Special Issue Research Article
Integrin-linked kinase regulates E-cadherin expression through PARP-1
Article first published online: 4 SEP 2008
Copyright © 2008 Wiley-Liss, Inc.
Special Issue: Special Focus on the Extracellular Matrix, in Memory of Dr. Elizabeth D. Hay
Volume 237, Issue 10, pages 2737–2747, October 2008
How to Cite
McPhee, T. R., McDonald, P. C., Oloumi, A. and Dedhar, S. (2008), Integrin-linked kinase regulates E-cadherin expression through PARP-1. Dev. Dyn., 237: 2737–2747. doi: 10.1002/dvdy.21685
- Issue published online: 24 SEP 2008
- Article first published online: 4 SEP 2008
- Manuscript Accepted: 25 JUN 2008
- epithelial to mesenchymal transition (EMT);
- integrin-linked kinase (ILK);
- Poly(ADP-ribose)polymerase (PARP);
Repression of E-cadherin expression by the transcription factor, Snail, is implicated in epithelial to mesenchymal transition and cancer progression. We show here that Integrin-Linked Kinase (ILK) regulates E-cadherin expression through Poly(ADP-ribose) polymerase-1 (PARP-1). ILK overexpression in Scp2 cells resulted in stimulation of Snail expression and loss of E-cadherin expression. Silencing of ILK, Akt or Snail resulted in re-expression of E-cadherin in PC3 cells. To elucidate the signaling pathway downstream of ILK, we identified candidate Snail promoter ILK Responsive Element (SIRE) binding proteins. PARP-1 was identified as a SIRE-binding protein. ILK silencing inhibited binding of PARP-1 to SIRE. PARP-1 silencing resulted in inhibition of Snail and ZEB1, leading to up-regulation of E-cadherin. We suggest a model in which ILK represses E-cadherin expression by regulating PARP-1, leading to the binding of PARP-1 to SIRE and modulation of Snail expression. Developmental Dynamics 237:2737–2747, 2008. © 2008 Wiley-Liss, Inc.