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Nat Rev Cancer. 2008 Nov;8(11):851-64. doi: 10.1038/nrc2501. Epub 2008 Oct 10.

Hypoxia signalling through mTOR and the unfolded protein response in cancer.

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  • 1Ontario Cancer Institute, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada. bwouters@uhnresearch.ca

Abstract

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.

PMID:
18846101
[PubMed - indexed for MEDLINE]
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