Abstract

In my brief introduction I will first describe the process of EMT and the reverse process MET. I will also summarise what is known about the role of EMT at various key stages of development, in particular gastrulation. Next I will provide a brief review of the roles EMT is hypothesized to play in cancer. Although most recent reviews seem to be unaware of this, there are a number of cell types in the body that are considered epithelial but express mesenchymal markers and may have the propensity to shift in either direction. These include the podocytes of the kidney, the mesothelial layer that lines various organs and the sertoli cells of the testis. These cells all express the tumour suppressor, WT1, which is vital for their structure and function. I will describe our recent work showing that WT1 is a key regulator of the mesenchyme to epithelial balance in a number of developing organs. In the kidney, WT1 is required for the MET that produces terminally differentiated nephron components. In the heart, WT1 is required for the EMT that generates proliferating coronary vascular progenitors for the epicardium. These divergent functions equate to WT1’s role as a tumour suppressor in childhood kidney cancer, but a postulated oncogene in adult cancers. WT1 functions mainly as a transcription factor and I will discuss briefly the molecular mechanisms by which it controls EMT or MET. Finally, I will summarise briefly our recent findings that WT1 is required for adult tissue homeostasis and repair, and put these findings in the context of mesenchymal biology.