Association of epithelial-mesenchymal transition and nuclear cofilin with advanced urothelial cancer

Patrick J. Hensley, Daniel Zetter, Craig M. Horbinski, Stephen E. Strup, Natasha Kyprianou*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)68-77
Number of pages10
JournalHuman pathology
Volume57
DOIs
StatePublished - Nov 1 2016

Keywords

  • Actin cytoskeleton
  • Bladder cancer
  • E-cadherin
  • N-cadherin
  • Phenotypic changes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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