Originally, the researchers were simply interested in studying the role of FOXO, a well-known transcription factor that functions as a genetic switch. It has been known for quite a while that the activation of FOXO enhances cellular stress resistance in many organisms. FOXO activity in the roundworm C. elegans actually doubles the animal’s lifespan. FOXO has also been shown to have tumor-suppressive properties. However, since in different varieties of leukemia FOXO may also have an opposite role, acting as an oncogene, a research group led by Dr. Wenjing Qi and Prof. Dr. Ralf Baumeister, two molecular geneticists from the University of Freiburg, decided to take a closer look at these contradicting results. For this purpose, they investigated the role of FOXO in cancer development using C. elegans, a tiny 1 millimeter long lab organism that is exceptionally suited to manipulate and analyze genetic functions.
The team of researchers discovered that activation of FOXO suffices to develop tumors in stem cells — omnipotent, immortal cells that have the capability of unlimited proliferation. When investigating the signals inducing this cancer, the scientists discovered that it could not be found in the tumor cells themselves, but came from the surrounding tissues — in this case, primarily from the epidermis. The researchers now hypothesize that erroneous signals from a neighboring tissue are being sent to the stem cells, which then develop into a tumor. The source of this signal not only involves several already known oncogenes, but several newly discovered genes. “With C. elegans, we were able to determine exactly which of the 20,000 genes in its genome are responsible for this tumor,” Qi explained. “We’ve already found more than 10 candidates and we’re still not done searching.” The team has now published part of their findings in the scientific journal PLoS Genetics. The publication is the result of a project in the Collaborative Research Center (SFB 850) called Control of Cell Motility in Morphogenesis, Cancer Invasion and Metastasis at the University of Freiburg.