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Bead Aggregation Assays for the Characterization of Putative Cell Adhesion Molecules
Published on: October 17, 2014
Integrin-linked kinase regulates E-cadherin expression through PARP-1
Timothy R McPhee1, Paul C McDonald, Arusha Oloumi
1Genetics Graduate Program, Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada.
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.
Insights
Integrin-Linked Kinase (ILK) controls E-cadherin expression via Poly(ADP-ribose) polymerase-1 (PARP-1). ILK regulates PARP-1 binding to the Snail promoter, impacting epithelial to mesenchymal transition and cancer progression.
Area of Science:
- Cell Biology
- Molecular Oncology
- Biochemistry
Background:
- E-cadherin repression by Snail is crucial for epithelial to mesenchymal transition (EMT) and cancer progression.
- Integrin-Linked Kinase (ILK) is a potential regulator of cellular processes involved in cancer.
Purpose of the Study:
- To elucidate the role of ILK in regulating E-cadherin expression.
- To identify the signaling pathway through which ILK affects E-cadherin and EMT.
Main Methods:
- Overexpression and silencing of ILK, Akt, and Snail in Scp2 and PC3 cell lines.
- Identification of Snail promoter ILK Responsive Element (SIRE) binding proteins using biochemical assays.
- Analysis of PARP-1 binding to SIRE and its effect on Snail and ZEB1 expression.
Main Results:
- ILK overexpression stimulated Snail expression and decreased E-cadherin.
- Silencing ILK, Akt, or Snail led to E-cadherin re-expression.
- PARP-1 was identified as a SIRE-binding protein; ILK silencing inhibited this binding.
- PARP-1 silencing reduced Snail and ZEB1, upregulating E-cadherin.
Conclusions:
- ILK represses E-cadherin expression by regulating PARP-1.
- PARP-1 binding to the Snail promoter (SIRE) is a key mechanism modulated by ILK.
- This ILK-PARP-1-Snail axis represents a novel regulatory pathway in EMT and cancer.
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