Inhibition of HIF prolyl hydroxylase-2 blocks tumor growth in mice through the antiproliferative activity of TGFβ

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

Abstract

Virtually all solid tumors are dependent on a vascular network to provide them with the right amount of nutrients and oxygen. In that sense, low oxygen tension or hypoxia leads to an adaptive response that is transcriptionally regulated by the hypoxia-inducible factors (HIF), which are tightly controlled by the HIF prolyl hydroxylases (PHD). In this study, we show that inhibition of the oxygen sensor PHD2 in tumor cells stimulates vessel formation but paradoxically results in a profound reduction of tumor growth. This effect relies on the antiproliferative nature of the TGFβ signaling pathway, in a largely HIF-independent manner. Moreover, our findings reveal that PHD2 has an essential function in controlling the dual nature of TGFb during tumorigenesis and may offer an alternative opportunity for anticancer therapy.

Details

Original languageEnglish
Pages (from-to)3306-3316
Number of pages11
JournalCancer research
Volume71
Issue number9
Publication statusPublished - 1 May 2011
Peer-reviewedYes

External IDs

PubMed 21436457
ORCID /0000-0001-7803-1972/work/142235112
ORCID /0000-0002-9467-780X/work/147674934

Keywords

ASJC Scopus subject areas