Supervisor: Prof. Dr. Stefan Hüttelmaier (Speaker of the GRK1591)
(1) The role of IGF2BP2 in controlling glucose homeostasis and diabetes
(2) The role of IGF2BP2 in growth control and tumor cell fate
Background and significance
One major class of RBPs associated with cancer and potentially diabetes is the IGF2 mRNA binding protein family (IGF2BPs). In humans, the IGF2BP family comprises three members, two of which, IGF2BP1 and IGF2BP3, are classified as oncofetal proteins with de novo synthesis in various solid cancers. In vitro studies suggest IGF2BP1 acts as a pro-metastatic oncogene promoting mesenchymal-like tumor cell properties including enforced migratory capacity as well as tumor cell survival. In contrast, the only family member observed in non-transformed adult mouse tissue, the IGF2BP2 paralogue, was suggested to modulate cell growth and glucose homeostasis. Genetic studies revealed that single nucleotide polymorphisms (SNPs) in the human IGF2BP2 gene are correlated with a modestly elevated risk of type 2 diabetes (T2D). In vitro, IGF2BP2 was shown to promote IGF2 mRNA translation in an mTOR-dependent manner. This suggests the protein to promote cell growth. However, in vivo validation of both, IGF2BP2-dependent control of glucose homeostasis and/or cell growth, is still lacking. Moreover, the molecular mechanisms and downstream effectors via which IGF2BP2 exerts its postulated regulatory roles remain largely elusive.