posters International Association for Breast Cancer Research 2014

Integrated Target Discovery in the EMPathy Breast Cancer Network - Multidimensional Analysis of Epithelial Mesenchymal Plasticity (EMP) in Experimental Systems. (#111)

Erik (Rik) W2 Thompson 1 2 3 , Melissa ? Davis 4 , Tony Blick 3 , Gayle Philip 5 , Eva Tomascovic-Crook 1 , Nick Wong 6 , Izhak Haviv 7 , EMPathy NBCF , Greg Goodall 8
  1. Invasion & Metastasis Unit, St. Vincent’s Institute, Melbourne , VIC, Australia
  2. University of Melbourne, Department of Surgery,St. Vincent’s Hospital, Melbourne , VIC, Australia
  3. IHBI and School of Biomedical Sciences, Queensland University of Technology and Translational Research Institute, Wooloongabba, QLD, Australia
  4. Systems and Computational Biology Laboratory, The University of Melbourne, Melbourne, VIC, Australia
  5. Victorian Life Sciences Computing Initiative, University of Melbourne , Melbourne, VIC, Australia
  6. Patho-Genomics, University of Melbourne Department of Pathology, Melbourne, VIC, Australia
  7. Faculty of Medicine in Galilee, Bar Ilan University, Zfat, Israel
  8. Centre for Cancer Biology, SA Pathology, Adelaide, SA, Australia

The ability of breast cancer cells to switch between epithelial and mesenchymal phenotypes may be key to their survival in new environments, resistance to therapies and ability to form metastases. Epithelial mesenchymal plasticity (EMP) is instrumental in embryological development and has been implicated in stemness, therapy resistance and metastasis of breast cancer. EMP markers are enriched in basal-like, triple negative breast cancer, which is a type of breast cancer associated with early recurrence and poor prognosis, and established as a common phenotype in women with BRCA1 mutations. The 7 thematic research projects of EMPathy BCN, including the 9 program-funded ‘Satellite’ projects, are aligned with the Cooperative Research Centre for Cancer Therapeutics (CTx) (www.cancercrc.com/index), so that any potential drug targets identified may progress into the CTx drug development program. Multiple parallel approaches in the Target Discovery theme were used to identify candidate regulators and effectors of EMP. A total of 10 functional or gene expression experiments provided 7,950 significant events in any one system, which were cross-referenced against 10 public breast cancer datasets relevant to EMP and/or breast cancer stem cells. A panel of 127 candidates were analysed in breast cancer tissues using Nanostring technology. 2,301 ‘significant events’ in any functional screen were further cross-referenced to 10 public functional datasets relevant to EMP in any system and a series of criteria were used to select a panel of 320 candidates that are to be analysed in an siRNA ‘functional screen’ of multiple breast cancer cell lines, to support the choice of Candidate Targets for drug development. Ongoing studies are address the biology behind selected candidates. This work and the EMPathy BCN is supported by a NBCF National Collaborative Research Program Grant.