Integrin-linked kinase regulates E-cadherin expression through PARP-1

✍ Scribed by Timothy R. McPhee; Paul C. McDonald; Arusha Oloumi; Shoukat Dedhar

• Book ID: 102818052
• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 958 KB
• Volume: 237
• Category: Article
• ISSN: 1058-8388
• DOI: 10.1002/dvdy.21685

✦ Synopsis

Abstract

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.