Project Title: The role of the tumor suppressor protein PTPN13 in epithelial cell polarization and tumor progression

Project supervisor: Dr Kai Erdmann (BMS and CMIAD)

Application deadline: Friday 14 December 2012.

Project description:

Cytokinesis is the final step of cell division. Increasing evidence suggests failure of cytokinesis might contribute to the development of cancer. We have previously shown that the tyrosine phosphatase PTPN13 is involved in the regulation of cytokinesis. Moreover, PTPN13 is a highly modular multi-PDZ domain protein composed of an N-terminal KIND (Kinase non catalytic C-lobe) domain, followed by a FERM (Four-point-one/Ezrin/Radixin/Moesin) domain, five PDZ domains, and a tyrosine phosphatase domain assembling a large macromolecular protein complex. There is strong evidence that PTPN13 plays a role in tumor development. In a search for protein tyrosine phosphatases involved in formation of colon carcinoma, it was demonstrated that PTPN13 is mutated in around 10% of colon carcinomas. We have recently shown that the serologically defined colon cancer antigen-3 (SDCCAG3) forms a complex with PTPN13. SDCCAG3 is a novel endosomal protein, primarily localized at the early/recycling endosomal compartment. We have also demonstrated that SDCCAG3 expression levels are elevated in colon cancers.

The goal of this project is to analyze the PTPN13/SDCCAG3 module with respect to cell migration and its relevance to metastasis and tumor invasion. Furthermore, using in vitro 3-dimensional cell culture systems and corresponding model organism (zebra fish) we will further analyze the role of PTPN13 in epithelial cell polarization.

Literature:

• Hagemann, N., Ackermann, N., Christmann, J., Brier, S, Yu, F., Erdmann, K.S.
  The serologically defined colon cancer antigen-3 interacts with the protein tyrosine phosphatase PTPN13 and is involved in the regulation of cytokinesis.
  Oncogene, in press
• Stenzel, N., Fetzer, C.P., Heumann, R., Erdmann, K.S.
  PDZ-domain directed basolateral targeting of peripheral membrane proteins in epithelial cells.
  J. Cell Sci., 122, 3374-3384 (2009)
• Freiss, G., Chalbos, D.
  PTPN13/PTPL1: an important regulator of tumor aggressiveness.
  Anticancer Agents Med Chem. 11, 77-88 (2011)

Contact details:

Dr Kai Erdmann

Email: K.Erdmann@sheffield.ac.uk

Web: http://www.sheffield.ac.uk/bms/research/erdmann/