The regulation of hybrid-EMT and metastasis in colorectal cancer

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Colorectal cancer is one of the commonest causes of cancer related death in the UK with metastasis (the spread of cancer cells to distant organs) the primary cause. For cancers to spread tumour cells need to invade into local tissues, break away from the primary tumour and then resettle at secondary sites. A process called epithelial to mesenchymal transition (EMT) is believed to be important for cancer spread but how it is controlled is poorly understood. This lack of knowledge impacts on our ability to develop new therapies that might inhibit it and provide benefit to patients.The purpose of this research is to try to understand how the EMT process is initiated and in particular how tumour cells are maintained in an intermediate state thought to be important for metastasis. We aim to investigate in detail the function of the genes we have identified that we think control this process and discover whether they are important for metastasis. We also aim to directly test if this process is found in aggressive human cancers and whether it can help predict patient outcome. Importantly, we will also attempt to identify candidate molecules that drive metastasis that could be inhibited by therapeutic drugs. Together, this research will lead to increased understanding of how colorectal cancer spreads. This could lead to important advances in how to manage the most aggressive forms of this disease and ultimately lead to new therapies for its treatment. Furthermore, since tumour metastasis is the primary cause of death in many other cancer types it could have far reaching implications for the treatment of other cancers as well.