Cited by 894Cancer, Hypoxia, and MetabolismPI3K/AKT/mTOR signaling in cancerAutophagy in Disease and Therapy

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Hypoxia signalling through mTOR and the unfolded protein response in cancer

Wouters, Bradly G., Koritzinsky, Marianne·2008·Nature Reviews Cancer

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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.

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Authors: Wouters, B. G., & Koritzinsky, M.
Affiliations: University Health Network (CA)
Corresponding author: Wouters, Bradly G.
ORCID: Wouters, Bradly G.
Koritzinsky, Marianne
Venue: Nature Reviews Cancer
Publisher: Springer Science and Business Media LLC
Published: 2008-10-10
Volume: 8
Issue: 11
Pages: 851-864
ISSN: 1474-175X (ISSN-L)
1474-1768
DOI: 10.1038/nrc2501
OpenAlex: W1978301900
Cited by: 894
References: 146
Citations by year: 2026: 16 · 2025: 47 · 2024: 27 · 2023: 30 · 2022: 31 · 2021: 48 · 2020: 39 · 2019: 56 · 2018: 54 · 2017: 46 · 2016: 62 · 2015: 63 · 2014: 68 · 2013: 66 · 2012: 73
FWCI: 4.00
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature reviews. Cancer (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
Keywords: hypoxia signaling, mTOR, unfolded protein response, hypoxia-inducible factor, tumor hypoxia, angiogenesis, metastasis, treatment resistance, cancer metabolism, carcinogenesis, tumor growth
MeSH terms: Humans, Neoplasms, Protein Kinases, Signal Transduction, Cell Hypoxia, Protein Folding, Hypoxia-Inducible Factor 1, alpha Subunit, TOR Serine-Threonine Kinases

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Hypoxia signalling through mTOR and the unfolded protein response in cancer

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