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

Authors

  • Timothy R. McPhee,

    1. Genetics Graduate Program, University of British Columbia, Vancouver, British Columbia, Canada
    2. Department of Cancer Genetics and Developmental Biology, British Columbia Cancer Research Centre, British Columbia Cancer Agency, Vancouver, British Columbia, Canada
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  • Paul C. McDonald,

    1. Department of Cancer Genetics and Developmental Biology, British Columbia Cancer Research Centre, British Columbia Cancer Agency, Vancouver, British Columbia, Canada
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    • Drs. McDonald and Oloumi contributed equally to the manuscript.

  • Arusha Oloumi,

    1. Department of Cancer Genetics and Developmental Biology, British Columbia Cancer Research Centre, British Columbia Cancer Agency, Vancouver, British Columbia, Canada
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    • Drs. McDonald and Oloumi contributed equally to the manuscript.

  • Shoukat Dedhar

    Corresponding author
    1. Genetics Graduate Program, University of British Columbia, Vancouver, British Columbia, Canada
    2. Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada
    3. Department of Cancer Genetics and Developmental Biology, British Columbia Cancer Research Centre, British Columbia Cancer Agency, Vancouver, British Columbia, Canada
    • British Columbia Cancer Research Centre, 675 W. 10th Avenue, Vancouver, British Columbia, Canada, V5Z 1L3
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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.

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