Unravelling the Mechanism of the Lung Tumour Suppressor LIMD1 from Cellular Metabolism to Malignant Transformation.

点击翻译按钮获取中文摘要

Lung cancer has a very poor survival rate; for disease to be detected earlier, and managed and treated better then more needs to be understood about how healthy cells are transformed into cancer cells.Our group has identified a gene called LIMD1 which prevents the transformation of normal, healthy cells into cancer. We have found that LIMD1 is lost from cells as they progress towards becoming cancerous and this is a key step in their transformation. Rapidly dividing cancer cells need a constant supply of energy and exciting new data from our lab have revealed that the loss of LIMD1 from cells affects the way they make this energy, a series of processes broadly called metabolism. Our project has been designed to thoroughly investigate the way in which loss of LIMD1 causes a switch from "normal" cell metabolism to a "cancerous" state. As well as needing a different amount and balance of nutrients, tumours have dramatically reduced supplies of oxygen and this is also linked to the way they adapt to changes in the requirement for energy. In this respect, we have previously shown that LIMD1 is required by cells to sense and adapt to the levels of oxygen around them. Therefore loss of LIMD1 in cancer cells will dramatically affect the way that they respond to changes in oxygen as tumours grow.To best observe the transformation of normal human lung tissue into cancer we have adopted a 3D model of a small portion of tissue representative of the human upper airways. Using this model we will seek to determine which pathways of metabolism LIMD1 loss affects and, importantly, if these pathways give us new markers of early stages of lung cancer and potential targets for chemotherapy.