Abstract
The intestinal epithelium – the cell wall that separates the intestinal tract from the rest of the body – is constantly renewed by intestinal stem cells that divide continuously. This process is under strict control to ensure that cell division and cell death are balanced, and that cells develop into the right type. Colon cancer occurs when this balance is disturbed. This is usually caused by DNA mutations in intestinal stem cells, causing them to escape normal control mechanisms and divide uncontrollably. Mutations can arise as a result of natural cell division, but they can also be exacerbated by external factors, such as inflammation and certain dietary patterns. The development of colon cancer is mainly driven by specific mutations in so-called driver genes, which strongly influence the behaviour of cells and genes.
To better understand colon tissue and cancer development, researchers use colonic organoids: cell structures that closely resemble healthy colon tissue and colon tumours. These can be grown in the lab, which makes it possible to manipulate specific components and measure their effects at molecular level. This PhD thesis describes various molecular processes involved in the development of healthy colon cells and colon cancer, as well as the methods that can be used to investigate these processes. We focus in particular on colon tumours with SMAD4 mutations, which are associated with aggressive tumours and an increased risk of metastases.
