Poster Presentation 14th International Biennial Conference on Metastasis Research 2012

Protein Tyrosine Phosphatase Pez - a novel regulator of Protein Trafficking and Secretion (#110)

X. Li 1 , L Belle 1 2 , N. Ali 3 , A. Lonic 1 , S. Roslan 1 , F. Gehling 1 , R. Daly 3 , Y. Khew-Goodall 1 2
  1. Center for Cancer biology, SA pathology, Adelaide, SA, Australia
  2. Discipline of Biochemistry, School of Molecular and Biomedical Sciences, the University of Adelaide, Adelaide, SA, Australia
  3. Cancer Research Programme, Garvan Institute of Medical Research, Sydney, NSW, Australia

We recently identified the protein tyrosine phosphatase Pez as a novel regulator of TGF-beta signalling and epithelial-mesenchymal transition (EMT)(Wyatt et al 2007). TGF-beta is a pleiotropic cytokine that plays opposing roles in cancer progression, acting early as a tumour suppressor, but promoting invasion and metastasis at later stages of carcinogenesis. Cancer-associated mutations in Pez have been identified in breast (Sjoblom et al, 2006) and colorectal cancers (Wang et al, 2004), however the role of such mutations in cancer progression remains unclear. Our recent data suggests that Pez is present in golgi / endosomal compartments in breast and other epithelial cells, modulates the secretion of multiple cytokines in addition to TGF-beta, and influences the trafficking of various signalling receptors. In an experimental mouse model of metastasis, reduced Pez expression leads to a specific increase in breast cancer metastasis to bone, suggesting Pez is a novel suppressor of bone metastasis. We hypothesise that deregulation of Pez expression or function in human cancers may lead to aberrant secretion of multiple factors into the tumour microenvironment to influence metastatic outcome. Ongoing studies aim to elucidate the specific molecular mechanisms by which Pez functions to exert these effects on secretion and cancer metastasis.

  1. Wyatt et al (2007) J. Cell Biol. 178: 1223-1235
  2. Sjoblom et al (2006) Science 314:268-74
  3. Wang et al (2004) Science 304:1164-6