The DOI matches its Crossref record; 146 of the 146 references it cites were found in a registry or an index.
Hypoxia signalling through mTOR and the unfolded protein response in cancer
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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“These adaptations include increased amino acid transporter activity and enzyme expression to boost the concentration of glutathione, the principal intracellular antioxidant, stimulation of hematopoiesis, and upregulation of the angiogenic growth factor VEGF.”
From Placental Origins of Chronic Disease (2016) · cites this paper as [585]
In the citing paper
“It also upregulates the transcription factor ATF4, which along with the ATF6 and IRE1 pathways selectively regulates gene expression to assist the cell to tolerate hypoxia (180, 343, 585).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [585]
In the citing paper
“There are two principal mechanisms that operate, a rapid response involving phosphorylation of eIF2α through PERK and the UPR, and a longer term response dependent on suppression of the mTOR pathway (181, 585).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [585]
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2 retracted
Mitochondrial Autophagy Is an HIF-1-dependent Adaptive Metabolic Response to Hypoxia
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RetractedProapoptotic BAX and BAK Modulate the Unfolded Protein Response by a Direct Interaction with IRE1α
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RetractedTargeting HIF-1 for cancer therapy
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Signal integration in the endoplasmic reticulum unfolded protein response
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Upstream and downstream of mTOR
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Autophagy: process and functionPreprint
Mizushima, N. (2007) · Genes & Development · doi:10.1101/gad.1599207 · Cited by 4,104
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
Endoplasmic Reticulum Stress Links Obesity, Insulin Action, and Type 2 Diabetes
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Metadata
- Authors
- Wouters, B. G., & Koritzinsky, M.
- Affiliations
- University Health Network (CA)
- Corresponding author
- Wouters, Bradly G.
- Venue
- Nature Reviews Cancer
- Published
- 2008-10-10
- Volume
- 8
- Issue
- 11
- Pages
- 851-864
- ISSN
- 1474-175X (ISSN-L)
- 1474-1768
- 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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