Project Title: Cell cycle dependent nuclear translocation of dystroglycan

Supervisor: Professor Steve Winder

Project Description:

Dystroglycan is a cell adhesion protein that is significantly reduced in advanced stages of cancers. Part of the mechanism underlying its loss is due to phosphorylation and subsequent proteolysis. In particular proteolysis generates an intracellular fragment that then translocates to the nucleus. Furthermore we have found in LNCaP prostate cancer cells that nuclear translocation is cell cycle dependent, and that nuclear translocation of dystroglycan also results in transcriptional changes in about 35 genes. Changes in dystroglycan during cancer progression may therefore be very important in determining the ability of cancer cells to grow, metastasise and colonise secondary sites.

This project will examine the mechanisms and consequences of dystroglycan nuclear translocation and identify the signals that trigger this cell cycle dependent event in LNCaP cells. Furthermore the potential role of some of the differentially regulated genes in this process will also be investigated.

References:

• Andrew Mitchell, Grinu Mathew, Jenny M Down, Taiwen Jiang Freddie C Hamdy, Colby Eaton, Simon S Cross, & Steve J Winder. Cancer Res (submitted)
  Dystroglycan function is a novel determinant of tumour growth and behaviour in prostate cancer. (email me for a copy)
• Parberry-Clark C, Bury JP, Cross SS, Winder SJ.
  Loss of dystroglycan function in oesophageal cancer.
  Histopathol 2011;59:180-7
• Singh J, Itahana Y, Knight-Krajewski S, et al.
  Proteolytic Enzymes and Altered Glycosylation Modulate Dystroglycan Function in Carcinoma Cells.
  Cancer Res 2004;64:6152-9

Contact Details:

Professor Steve Winder

http://www.sheffield.ac.uk/bms/research/winder

Email: s.winder@sheffield.ac.uk