Poster Presentation 26th Lorne Cancer Conference 2014

High content screening for inhibitors of epithelial-to-mesenchymal transitions in breast cancer (#201)

Karl-Johan Leuchowius 1 , Cletus Pinto 1 , Kurt Lackovic 1 , Erik Thompson 1 , Ian Street 1
  1. Walter and Eliza Hall Institute of Medical Research, Bundoora, VIC, Australia

Metastasis is the leading cause of death among breast cancer patients, and drugs targeting metastatic processes are much needed. One such process is the epithelial-to-mesenchymal transition (EMT), with which epithelial cells gain mesenchymal properties such as increased motility and the ability to invade surrounding tissue. In addition to phenotypic changes, EMT is characterised by downregulation of epithelial biomarkers such as E-cadherin, and upregulation of mesenchymal biomarkers such as Vimentin. EMT has been found to be induced in several different ways, including stimulation with growth factors such as TGFβ, EGF and HGF, but also by cellular stresses such as hypoxia or radiation. We have developed a high content screening assay for inhibitors and inducers of EMT, and have used it to screen a set of focused libraries of small molecules in breast cancer cell lines. Our goal with the screens was to increase our knowledge about the target biology through a chemical biology approach, as well as trying to discover opportunities for drug repurposing.