Merkel cell polyomavirus small T antigen mediates microtubule destabilization to promote cell motility and migration

Research output: Contribution to journalArticle

Authors

  • Laura M. Knight
  • Gabriele Stakaityte
  • Jennifer J. Wood
  • Hussein Abdul-Sada
  • David A. Griffiths
  • Gareth J. Howell
  • G. Eric Blair
  • Andrew Macdonald
  • David J. Blackbourn
  • Adrian Whitehouse

Colleges, School and Institutes

External organisations

  • University of Leeds
  • SURREY UNIVERSITY

Abstract

Merkel cell carcinoma (MCC) is an aggressive skin cancer of neuroendocrine origin with a high propensity for recurrence and metastasis. Merkel cell polyomavirus (MCPyV) causes the majority of MCC cases due to the expression of the MCPyV small and large tumor antigens (ST and LT, respectively). Although a number of molecular mechanisms have been attributed to MCPyV tumor antigen-mediated cellular transformation or replication, to date, no studies have investigated any potential link between MCPyV T antigen expression and the highly metastatic nature of MCC. Here we use a quantitative protesomic approach to show that MCPyV ST promotes differential expression of cellular proteins implicated in microtubule-associated cytoskeletal organization and dynamics. Intriguingly, we demonstrate that MCPyV ST expression promotes microtubule destabilization, leading to a motile and migratory phenotype. We further highlight the essential role of the microtubule-associated protein stathmin in MCPyV ST-mediated microtubule destabilization and cell motility and implicate the cellular phosphatase catalytic subunit protein phosphatase 4C (PP4C) in the regulation of this process. These findings suggest a possible molecular mechanism for the highly metastatic phenotype associated with MCC.

Details

Original languageEnglish
Pages (from-to)35-47
Number of pages13
JournalJournal of virology
Volume89
Issue number1
Early online date15 Oct 2014
Publication statusPublished - Jan 2015

ASJC Scopus subject areas