8th Annual Symposium
Physics of Cancer
October 4-6, 2017
|PoC - Physics of Cancer - Annual Symposium|
Regulation of Actin Cytoskeleton during Epithelial to Mesenchymal Transition - The Ocular Lens Perspective
McMaster University, Department of Pathology and Molecular Medicine, 1280 Main Street West, L8S4L8, Hamilton, Ontario, Canada
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Posterior Capsular opacification (PCO) or secondary cataract is the pathology of the ocular lens that results from transformation of remnant lens epithelial cells to mesenchymal cells following primary cataract surgery. Previous studies have implicated transforming growth factor (TGF)-β-induced epithelial-mesenchymal transition (EMT) of lens epithelial cells to be the major cause of PCO. Features of transformed lens epithelial cells include extensive cytoskeletal remodeling, including downregulation of epithelial cadherin (E-cadherin), F-actin polymerization and upregulation of α-smooth muscle actin (α-SMA). We have previously demonstrated the role of matrix metalloproteinase 9 (MMP-9) in the induction of TGF-β-induced lens fibrosis. Further, we have also shown that TGF-β-induced remodeling of the actin cytoskeleton is mediated through Rho- and β-catenin-signaling cascade. In addition, our work also suggests that myocardin related transcription factor A (MRTF-A), an actin-binding protein, is an important mediator of TGF-β-induced EMT in the lens. We are now extending our studies to understand the interplay between these key signaling molecules (MMP-9, Rho kinase, β-catenin and MRTF-A) during TGF-β-induced EMT in the lens. Together, our results demonstrate that these key signaling molecules act in conjunction with each other and reveal unexpected interaction during the progression of secondary cataract.