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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Mitochondrial Autophagy Is an HIF-1-dependent Adaptive Metabolic Response to Hypoxia
Zhang, H., Bosch-Marce, M., Shimoda, L. A., Tan, Y. S., Baek, J. H., Wesley, J. B., Gonzalez, F. J., & Semenza, G. L. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m800102200 · Cited by 1,601
Retracted
Proapoptotic BAX and BAK Modulate the Unfolded Protein Response by a Direct Interaction with IRE1α
Hetz, C. A., Bernasconi, P., Fisher, J. K., Lee, A., Bassik, M. C., Antonsson, B. E., Brandt, G. S., Iwakoshi, N. N., Schinzel, A. C., Glimcher, L. H., et al. (2006) · Science · doi:10.1126/science.1123480 · Cited by 688
Retracted
Targeting HIF-1 for cancer therapy
Semenza, G. L. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1187 · Cited by 6,717
Signal integration in the endoplasmic reticulum unfolded protein response
Ron, D., & Walter, P. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2199 · Cited by 6,431
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Hay, N., & Sonenberg, N. (2004) · Genes & Development · doi:10.1101/gad.1212704 · Cited by 4,181
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The Biology of Cancer: Metabolic Reprogramming Fuels Cell Growth and Proliferation
DeBerardinis, R. J., Lum, J. J., Hatzivassiliou, G., & Thompson, C. B. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2007.10.002 · Cited by 4,088
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Özcan, U., Cao, Q., Yilmaz, E., Lee, A.-H., Iwakoshi, N. N., Özdelen, E., Tuncman, G., Görgün, C., Glimcher, L. H., & Hotamisligil, G. S. (2004) · Science · doi:10.1126/science.1103160 · Cited by 3,844
An Integrated Stress Response Regulates Amino Acid Metabolism and Resistance to Oxidative Stress
Harding, H. P., Zhang, Y., Zeng, H., Novoa, I., Lu, P. D., Calfon, M. A., Sadri, N., Yun, C., Popko, B., Paules, R. S., et al. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00105-9 · Cited by 3,336
Defining the role of mTOR in cancer
Guertin, D. A., & Sabatini, D. M. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.05.008 · Cited by 2,833

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Rouschop, K. M. A., van den Beucken, T., Dubois, L., Niessen, H., Bussink, J., Savelkouls, K., Keulers, T., Mujcic, H., Landuyt, W., Voncken, J. W., et al. (2010) · Journal of Clinical Investigation · doi:10.1172/jci40027 · Cited by 829
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Chen, X., Iliopoulos, D., Zhang, Q. H., Tang, Q., Greenblatt, M. B., Hatziapostolou, M., Lim, E., Tam, W. L., Ni, M., Chen, Y., et al. (2014) · Nature · doi:10.1038/nature13119 · Cited by 840
The unfolded protein response in immunity and inflammation
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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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