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Hypoxia signalling in cancer and approaches to enforce tumour regression
Abstract
Tumour cells emerge as a result of genetic alteration of signal circuitries promoting cell growth and survival, whereas their expansion relies on nutrient supply. Oxygen limitation is central in controlling neovascularization, glucose metabolism, survival and tumour spread. This pleiotropic action is orchestrated by hypoxia-inducible factor (HIF), which is a master transcriptional factor in nutrient stress signalling. Understanding the role of HIF in intracellular pH (pH(i)) regulation, metabolism, cell invasion, autophagy and cell death is crucial for developing novel anticancer therapies. There are new approaches to enforce necrotic cell death and tumour regression by targeting tumour metabolism and pH(i)-control systems.
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“The affinity of PHDs and FIH-1 for oxygen differs and, since FIH-1 has a higher affinity (lower K m ) for oxygen, PHDs are thought to be more rapidly inhibited in low oxygen conditions (Pouyssegur et al., 2006).”
From Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer (2016) · cites this paper as Pouyssegur et al., 2006
In the citing paper
“this is recognized to have profound effects on the tumor metabolism (92)(93)(94)”
From Adipose tissue remodeling and obesity (2011) · cites this paper as [93]
In the citing paper
“O 2 tension in the center of solid tumors may be so low that cells essentially become anoxic”
From Adipose tissue remodeling and obesity (2011) · cites this paper as [93]
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Metadata
- Authors
- Pouysségur, J., Dayan, F., & Mazure, N. M.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Pouysségur, Jacques
- Venue
- Nature
- Published
- 2006-05-24
- Volume
- 441
- Issue
- 7092
- Pages
- 437-443
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2082483448
- Semantic Scholar
- 5bbdcf74ee4cdf263a532b6dbae0b8dd5efb9722
- Cited by
- 1,676
- References
- 104
- Citations by year
- 2026: 19 · 2025: 39 · 2024: 48 · 2023: 75 · 2022: 85 · 2021: 97 · 2020: 87 · 2019: 77 · 2018: 81 · 2017: 68 · 2016: 85 · 2015: 80 · 2014: 103 · 2013: 104 · 2012: 89
- FWCI
- 6.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Ligue Contre le Cancer
- Centre National de la Recherche Scientifique
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Ferroptosis and cancer prognosis
- Keywords
- hypoxia signaling, hypoxia-inducible factor, tumor hypoxia, tumor regression, cancer metabolism, intracellular pH regulation, tumor angiogenesis, glucose metabolism, necrosis, autophagy, cell invasion, cancer therapy, tumor oxygenation
- MeSH terms
- Animals, Humans, Neoplasms, Neovascularization, Pathologic, Oxygen, Protein Kinases, Signal Transduction, Cell Hypoxia, TOR Serine-Threonine Kinases
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