Activin and Transforming Growth Factor beta signaling; crosstalk and divergence in colorectal cancer

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Colorectal cancer (CRC) is the third most common cancer in worldwide and was the cause of 17.000 deaths in Germany in 2013. The overall number of cases and the number of deaths due to CRC is declining, mostly due to earlier detection through better screening efforts. Still, survival rates once the tumor has spread to other organs remain poor. To date, treatment for advanced CRC does not cure the patient, and new treatment options are desperately needed. Transforming growth factor beta (TGF-beta) is a well-studied factor in colorectal cancer and a hopeful candidate as a future treatment target. Another related protein which is much less well understood but not less important is Activin. Activin and TGF-beta signaling pathways share members, and are thought to be beneficial in some cases, but harmful in others. Besides similarities and connections, the crossplay between the two has not been thoroughly studied in CRC yet. We hypothesize that in order to truly understand the Activin/TGF-beta system it has to be seen as a functional unit. In this project, we will investigate the relationship between these two signaling molecules by using a number of different approaches, including analysis of mutations in CRC through database queries, cell culture experiments, different mouse models and the analysis of Activin and TGF-beta in human samples. Taken together, data obtained throughout this project will change the view on two of the most important signaling pathways in colorectal cancer. Truly understanding the Activin/TGF-beta signaling network will be an unavoidable step towards designing new biomarkers and providing new treatment options for one of the world`s leading causes of cancer related mortality.