Activins and follistatins in tumor progression

Activins represent a subgroup within the large Transforming Growth Factor beta (TGFbeta) family  of cytokines and are intricately involved in the differentiation of embryonic stem cells, in reproductive biology and in tissue homeostasis. In the liver they are potent inducers of cell death whereas in other organs they have a cytoprotective function. Consequently during tumor development and progression we observe either increased activin signaling activity for instance in mesothelioma or a decrease in activin signals through upregulation of antagonistic follistatin proteins for instance in hepatocellular carcinoma. Our aim is to understand their pro- and anti-oncogenic roles in malignancy with respect to potential therapeutic or diagnostic applications.

Figure: Activin signaling and interaction points with activin antagonists. A: Activins first bind type II activin receptors, which then recruit and phosphorylate type I receptors. These in turn phosphorylate receptor-activated Smads, which subsequently form a complex with Smad 4 and translocated to the nucleus, where they regulate the transcription of target genes; B: Activin antagonists can block activin signals by: (1) binding activins in the extracellular space, (2) acting as inhibitory co-receptors, or (3) competing with receptor-activated Smads (figure taken from Deli et al 2008).

Students: Elisabeth Lang

Collaborations: The Thoracic Oncology Lab (Balazs Hegedüs, Balazs Döme, Mir Alireza Hoda, Division of Thoracic Surgery, Medical University of Vienna)

Financial support: Herzfelder Foundation, Vienna Fund for Innovative Interdisciplinary Cancer Research
 

Research Focus: Development of Experimental Cancer Therapies, Tumor Progression and Metastasis