Abstract:
: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.
journal_name
Cancer Biol Therjournal_title
Cancer biology & therapyauthors
Klotzsche-von Ameln A,Muschter A,Heimesaat MM,Breier G,Wielockx Bdoi
10.4161/cbt.13.4.18830subject
Has Abstractpub_date
2012-02-15 00:00:00pages
216-23issue
4eissn
1538-4047issn
1555-8576pii
18830journal_volume
13pub_type
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