Role of nucleoside diphosphate kinases in primary tumors and metastases of renal cell carcinoma
Matthias Schwab & Elke Schäffeler

There is increasing evidence that G protein-mediated processes play an important role in development and metastasis formation of various cancer entities, including renal cell carcinoma (RCC). Recently, members of the non-mitochondrial nucleoside diphosphate kinase (NDPK) class I isoforms, have been shown to lead to the non-canonical activation of G proteins that serve as proto-oncogenes in several types of cancer. The human NDPK family currently comprises at least ten different members. NDPK proteins have previously been linked to unique alterations in nucleotide metabolism in RCC compared to other cancer entities. However, research on the impact of the NDPK family on non-canonical G protein-mediated signaling in RCC is so far limited.

The underlying mechanism and functional consequences of variable NDPK expression and the activation of non-canonical G protein-mediated signaling for RCC development and metastases are elusive. Thereby, the present project will investigate functional consequences of selected NDPK isoforms (encoded by NME1 to 4) expressed in primary RCC and distant metastases. Furthermore, we aim to study translational aspects to elucidate the potential of NDPK isoforms as novel targets for RCC therapy.