HIF prolyl hydroxylase-2 inhibition diminishes tumor growth through matrix metalloproteinase-induced TGFβ activation.

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 Ther

journal_title

Cancer biology & therapy

authors

Klotzsche-von Ameln A,Muschter A,Heimesaat MM,Breier G,Wielockx B

doi

10.4161/cbt.13.4.18830

subject

Has Abstract

pub_date

2012-02-15 00:00:00

pages

216-23

issue

4

eissn

1538-4047

issn

1555-8576

pii

18830

journal_volume

13

pub_type

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