title: Association of epithelial-mesenchymal transition and nuclear cofilin with advanced urothelial cancer.
abstract: Tumor epithelial cells undergo a morphologic shift through the process of EMT with characteristic loss of cell polarity, conferring invasive and metastatic properties during cancer progression. Signaling by transforming growth factor-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 toward establishing an EMT signature in human bladder cancer. Serial sections were assessed for the primary regulator of the actin cytoskeleton remodeling and transforming growth factor-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.
authors.affiliation: Department of Urology, University of Kentucky College of Medicine, Lexington, KY 40536; Department of Pathology, University of Kentucky College of Medicine, Lexington, KY 40536.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Hensley
authors.affiliation: Department of Urology, University of Kentucky College of Medicine, Lexington, KY 40536.
authors.forename: Daniel
authors.initials: D
authors.lastname: Zetter
authors.affiliation: Department of Pathology, University of Kentucky College of Medicine, Lexington, KY 40536; Departments of Pathology and Neurosurgery, Northwestern University, Chicago, IL 60611.
authors.forename: Craig M
authors.initials: CM
authors.lastname: Horbinski
authors.affiliation: Department of Urology, University of Kentucky College of Medicine, Lexington, KY 40536.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Strup
authors.affiliation: Department of Urology, University of Kentucky College of Medicine, Lexington, KY 40536; Department of Pathology, University of Kentucky College of Medicine, Lexington, KY 40536; Department of Molecular Biochemistry, University of Kentucky College of Medicine, Lexington, KY 40536; Department of Toxicology & Cancer Biology, University of Kentucky College of Medicine, Lexington, KY, 40536. Electronic address: nkypr2@email.uky.edu.
authors.forename: Natasha
authors.initials: N
authors.lastname: Kyprianou
mesh_terms: D008841:Actin Cytoskeleton / Q000737:chemistry / Q000473:pathology; D015703:Antigens, CD / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D015820:Cadherins / Q000032:analysis; D002277:Carcinoma / Q000737:chemistry* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D002467:Cell Nucleus / Q000737:chemistry* / Q000473:pathology; D051338:Cofilin 1 / Q000032:analysis* / Q000235:genetics; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D007150:Immunohistochemistry; D060787:Neoplasm Grading; D012333:RNA, Messenger / Q000235:genetics; D012189:Retrospective Studies; D059016:Tumor Microenvironment; D001749:Urinary Bladder Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D019459:Urothelium / Q000737:chemistry* / Q000473:pathology
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; C513384:CDH1 protein, human; C050361:CDH2 protein, human; C495810:CFL1 protein, human; D015820:Cadherins; D051338:Cofilin 1; D012333:RNA, Messenger
keywords: Actin cytoskeleton; Bladder cancer; E-cadherin; N-cadherin; Phenotypic changes