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

结直肠癌（CRC）是全球第三大常见癌症，2013年在德国造成1.7万人死亡。结直肠癌的总病例数和死亡人数正在下降，这主要是由于通过更好的筛查工作及早发现。然而，一旦肿瘤扩散到其他器官，生存率仍然很低。迄今为止，晚期结直肠癌的治疗并不能治愈患者，迫切需要新的治疗方案。转化生长因子β (tgf - β)是一种被广泛研究的结直肠癌因子，有望成为未来的治疗靶点。另一种与之相关的蛋白质我们对它的了解要少得多，但同样重要，那就是激活蛋白。激活素和tgf - β信号通路共享成员，并且被认为在某些情况下是有益的，但在其他情况下是有害的。除了相似和联系之外，两者之间的交叉作用在CRC中还没有得到深入的研究。我们假设，为了真正理解激活素/ tgf - β系统，它必须被视为一个功能单元。在这个项目中，我们将通过使用多种不同的方法来研究这两种信号分子之间的关系，包括通过数据库查询分析CRC突变，细胞培养实验，不同的小鼠模型以及分析人类样本中的激活素和tgf - β。综上所述，在整个项目中获得的数据将改变对结直肠癌中两个最重要的信号通路的看法。真正了解激活素/ tgf - β信号网络将是设计新的生物标志物和为世界上癌症相关死亡的主要原因之一提供新的治疗选择的不可避免的一步。

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.