Authors: Anne Klotzsche-von Ameln, Antje Muschter, Markus M. Heimesaat, Georg Breier and Ben Wielockx

Anne Klotzsche-von Ameln

Institute of Pathology; University of Technology; Dresden, Germany; Emmy Noether Research Group; University of Technology; Dresden, Germany

Antje Muschter

Institute of Pathology; University of Technology; Dresden, Germany; Emmy Noether Research Group; University of Technology; Dresden, Germany

Markus M. Heimesaat

Institute for Microbiology and Hygiene; Charité—University of Medicine; Berlin, Germany

Georg Breier

Institute of Pathology; University of Technology; Dresden, Germany; DFG Research Center and Cluster of Excellence for Regenerative Therapies; University of Technology; Dresden, Germany

Ben Wielockx

Corresponding author: Ben.Wielockx@uniklinikum-dresden.de
Institute of Pathology; University of Technology; Dresden, Germany; Emmy Noether Research Group; University of Technology; Dresden, Germany

A right amount of oxygen and nutrients is essential for a tumor to develop. The role of oxygen dependent pathways and their regulators is therefore of utmost importance although little is known about the detailed impact they can have. Recently we have shown that inhibition of the oxygen sensor PHD2 in tumor cells blocks tumor growth due to the anti-proliferative activity of TGFβ. In this study, we refined these results by comparing different shPHD2 sequences in depth in the early phase of tumor growth. Our findings also reveal an intriguing role for MMP2 and MT1MMP in these settings, as these activated proteases display an anti-proliferative characteristic through the activation of downstream TGFβ targets. In conclusion, PHD2 inhibition is essential for the regulation of the anti-tumoral activity in mouse tumor cells and might bring some new insight in our understanding of tumor growth inhibition.