Tumor epithelial cells undergo a morphological shift through the process of epithelial mesenchymal transition (EMT) with characteristic loss of cell polarity, conferring invasive and metastatic properties during cancer progression. Signaling by transforming growth factor-β (TGF-β) mediates EMT programming and its phenotypic reversal to mesenchymal-epithelial transition. The role of EMT in bladder cancer progression to advanced disease is poorly understood. In this study we conducted a retrospective analysis of the EMT landscape and actin cytoskeleton remodeling in a series of human bladder cancer specimens. Immunoreactivity for E-cadherin, N-cadherin, and vimentin protein expression was performed towards establishing an EMT signature in human bladder cancer. Serial sections were assessed for the primary regulator of the actin cytoskeleton remodeling and TGF-β signaling effector, cofilin. Our results demonstrate that EMT induction in clinical bladder cancer specimens is significantly associated with bladder cancer progression to high grade, invasive disease. Evaluation of expression and cellular localization of the cytoskeleton regulator cofilin revealed a significant association between overexpression of nuclear cofilin with bladder cancer progression. This study is of translational significance in defining the value of EMT signature and cytoskeletal cofilin as potential tumor markers and targetable platforms for the treatment of invasive bladder cancer.
Human pathology. 2016 Jul 08 [Epub ahead of print]
Patrick J Hensley, Daniel Zetter, Craig M Horbinski, Stephen E Strup, Natasha Kyprianou
Department of Urology, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY, USA, 40536; Department of Pathology, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY, USA, 40536., Department of Urology, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY, USA, 40536., Department of Pathology, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY, USA, 40536; Departments of Pathology and Neurosurgery, Northwestern University, 300 East Superior Street, Chicago, IL, USA, 60611., Department of Urology, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY, USA, 40536., Department of Urology, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY, USA, 40536; Department of Pathology, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY, USA, 40536; Department of Molecular Biochemistry, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY, USA, 40536; Department of Toxicology & Cancer Biology, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY, USA, 40536. Electronic address: .