The role of MINK1 in homoeostasis of the intestinal epithelium (360G-Wellcome-203962_Z_16_A)

Surgery and chemotherapy, which preferentially kills dividing cells, are the main treatments for colon cancer: a common disease in the developed world. To develop better treatments requires defining the molecular events that cause tumours to grow so that these specific aberrations can be bypassed. Mutations in a gene called Adenomatous polyposis coli (Apc) are the most common molecular change identified in colon tumours. The Näthke lab recently discovered that APC protein (encoded by the Apc gene) binds to and regulates the abundance of another protein (MINK1) with roles in cell division and movement. This raises the possibility that faulty control of MINK1 by mutated APC could explain why cells in colon tumours divide excessively and migrate aberrantly. I will investigate the function and control of MINK1. Using cells grown in dishes and also cells that form mini-gut structures called organoids, experiments will be designed to determine whether and how MINK1 is required for Apc mutations to cause cancer, and how MINK1 affects the structure of the gut lining. These issues will also be addressed in mice whose guts lack the Mink1 gene. Results will help to decide whether human colon cancer can be treated by new drugs that target MINK1.