Journal
NATURE REVIEWS CANCER
Volume 8, Issue 11, Pages 851-864Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nrc2501
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Funding
- Dutch Science Organization (ZonMW-NWO Top) [912-03-047]
- VENI [916.56.015]
- Dutch Cancer Society (KWF) [UM 2003-2821]
- EU 6th framework programme (Euroxy programme)
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Hypoxia occurs in the majority of tumours, promoting angiogenesis, metastasis and resistance to therapy. Responses to hypoxia are orchestrated in part through activation of the hypoxia-inducible factor family of transcription factors (HIFs). Recently, two additional O-2-sensitive signalling pathways have also been implicated: signalling through the mammalian target of rapamycin (mTOR) kinase and signalling through activation of the unfolded protein response (UPR). Although they are activated independently, growing evidence suggests that HIF-, mTOR- and UPR-dependent responses to hypoxia act in an integrated way, influencing each other and common downstream pathways that affect gene expression, metabolism, cell survival, tumorigenesis and tumour growth.
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