期刊
CANCER BIOLOGY & THERAPY
卷 13, 期 4, 页码 -出版社
LANDES BIOSCIENCE
DOI: 10.4161/cbt.13.4.18830
关键词
HIF prolyl hydroxylase-2 (PHD2); hypoxia; matrix metalloproteinases; TGFbeta
类别
资金
- Fonds voor Wetenschappelijk Onderzoek-Vlaanderen (FWO, Belgium)
- Bundesministerium fur Bildung und Forschung (BMBF, Germany)
- Deutsche und Forschungsgemeinschaft (DFG, Germany) [WI 3291/1-1, Br1336/3-1, Br1336/3-2, SPP 1190]
- BMBF
- Emmy Noether fellow (DFG)
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 antiproliferative activity of TGF beta. 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 TGF beta 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.
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