Integrated Target Discovery in the EMP<em>athy</em> Breast Cancer Network - Multidimensional Analysis of Epithelial Mesenchymal Plasticity (EMP) in Experimental Systems. — ASN Events
  1. Schedule
  2. Poster discussion 1
  3. Integrated Target Discovery in the EMPathy Breast Cancer Network - Multidimensional Analysis of Epithelial Mesenchymal Plasticity (EMP) in Experimental Systems.

Integrated Target Discovery in the EMPathy Breast Cancer Network - Multidimensional Analysis of Epithelial Mesenchymal Plasticity (EMP) in Experimental Systems. (#236)

Melissa Davis 1 , Elizabeth D Williams 2 3 , Tony Blick 3 , Gayle Philip 4 , Eva Tomascovic-Crook 5 , Nick Wong 6 , Izhak Haviv 7 8 , Kaylene Simpson 9 , EMPathy BCN 10 , Gregory Goodall 11 , Erik (Rik) W Thompson 3 5 12
  1. Systems and Computational Biology Laboratory, The University of Melbourne, Melbourne, VIC, Australia
  2. Australian Prostate Cancer Research Centre – QLD, Translational Research Institute, Melbourne
  3. IHBI and School of Biomedical Sciences, Queensland University of Technology and Translational Research Institute, Wooloongabba, QLD, Australia
  4. Victorian Life Sciences Computing Initiative, University of Melbourne , Melbourne, VIC, Australia
  5. Invasion & Metastasis Unit, St. Vincent’s Institute, Melbourne , VIC, Australia
  6. Translational Genomics & Epigenomics Laboratory, Olivia Newton-John Cancer & Wellness Centre, Melbourne
  7. Faculty of Medicine in Galilee, Bar Ilan University, Zfat, Israel
  8. Patho-Genomics, University of Melbourne Department of Pathology, Melbourne, VIC, Australia
  9. Victorian Centre for Functional Genomics, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
  10. http://www.mtci.com.au/TEMTIA/EMPathy.html, IHBI, QUT, Brisbane
  11. Centre for Cancer Biology, SA Pathology, Adelaide, SA, Australia
  12. University of Melbourne, Department of Surgery,St. Vincent’s Hospital, Melbourne , VIC, Australia

Epithelial mesenchymal plasticity (EMP) is instrumental in embryological development and has been implicated in stemness, therapy resistance and metastasis of breast cancer (BC). EMP markers are elevated in basal-like, triple negative BC, which are over-represented in women with BRCA1 mutations and are associated with early recurrence and poor prognosis. The EMPathy Breast Cancer Network (BCN) is a national collaborative effort including scientists clinicians and a consumer advocate investigating the role of EMP in BC recurrence. The 7 thematic research projects and 9 program Satellite projects of EMPathy BCN are aligned with the Cooperative Research Centre for Cancer Therapeutics (CTx) (www.cancercrc.com/index), so that 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 were cross referenced against 10 public BC datasets relevant to EMP and/or BC stem cells. A series of criteria were used to select a panel of 127 candidates that were combined with 123 ad hoc candidates (mainly hits close to the cut-off and breast cancer context genes) to give a total of 250 candidates to be analysed in breast cancer tissues using Nanostring technology. The 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 were analysed in an siRNA ‘functional screen’ of multiple BC cell lines, to support the choice of candidate targets for drug development. Several candidates have emerged and are being pursued. In particular, a strong underpinning of the TGFβ signaling pathway has been revealed, which may be held in check by IRS1.  The EMPathy BCN is supported by an NBCF National Collaborative Research Program Grant.

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