Epithelial cells are a specialised cell type that line most body surfaces and cavities, such as the skin, intestine and lungs. These cells have an interesting structure; the top (or “apicalâ€) part of the cells consists of very different molecular components from the bottom, (or “basalâ€) part. This feature is called “cell polarityâ€.
In tumours that develop from epithelial cells, this polarity is lost, but how the loss of polarity leads to cancer is not understood. Many of the proteins that control cell polarity were first identified in the fly. Lethal giant larvae (Lgl), Scribble and Discs large (Dlg) are three such polarity regulators. When flies have mutations in these proteins, epithelial cells lose their polarity and tumours develop. These fly tumours have many similarities to human cancers, in that the tumour cells show unrestrained growth and an increased ability to move and invade other tissues. Lgl, Scribble and Dlg appear to function as cellular scaffolds, binding other proteins in a highly regulated fashion. The aim of my project is to identify novel binding partners for these polarity proteins in human cells and to determine the function and regulation of these interactions. I start by extracting polarity proteins from cells or tissues and find out what other proteins are bound to them. To do this, I use a technique called mass spectrometry, which allows us to identify proteins by breaking them into small pieces and measuring the mass of these fragments very accurately. I am currently confirming some of the binding partners I have identified. I will then determine the function of the interactions; whether they regulate cell structure, the movement of proteins of within the cell or cell growth for example, and then see how these interactions change in tumour cells.
