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The hypoxic tumour microenvironment and metastatic progression
Abstract
The microenvironment of solid tumours contains regions of poor oxygenation and high acidity. Growing evidence from clinical and experimental studies points to a fundamental role for hypoxia in metastatic progression. Prolonged hypoxia increases genomic instability, genomic heterogeneity, and may act as a selective pressure for tumour cell variants. Hypoxia can also act in an epigenetic fashion, altering the expression of genes. Hypoxia-induced changes in gene expression alter non-specific stress responses, anaerobic metabolism, angiogenesis, tissue remodeling, and cell-cell contacts. Experimental studies have demonstrated that inhibition of proteins involved in these processes can modify metastasis formation, suggesting a causal role in metastatic progression. Recent advances in high-throughput screening techniques have allowed identification of many hypoxia-induced genes that are involved in the processes associated with metastasis. Here we review the epigenetic control of gene expression by the hypoxic microenvironment and its potential contribution to metastatic progression.
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“Exposing cancer cells to hypoxia ex vivo is known to increase lung colonization after intravenous injection [34].”
From The hypoxic tumor microenvironment: A driving force for breast cancer progression (2016) · cites this paper as [34]
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Metadata
- Authors
- Subarsky, P., & Hill, R. P.
- Affiliations
- University of Toronto (CA)
- Corresponding author
- Hill, Richard P.
- ORCID
- Hill, Richard P.
- Venue
- Clinical & Experimental Metastasis
- Published
- 2003-05
- Volume
- 20
- Issue
- 3
- Pages
- 237-250
- ISSN
- 0262-0898 (ISSN-L)
- 1573-7276
- OpenAlex
- W122518273
- Cited by
- 327
- References
- 132
- Citations by year
- 2026: 1 · 2024: 2 · 2023: 7 · 2022: 8 · 2021: 12 · 2020: 10 · 2019: 9 · 2018: 4 · 2017: 23 · 2016: 17 · 2015: 12 · 2014: 14 · 2013: 17 · 2012: 9
- FWCI
- 7.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Clinical & Experimental Metastasis (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Keywords
- tumor hypoxia, tumor microenvironment, metastatic progression, genomic instability, genomic heterogeneity, epigenetic regulation, hypoxia-induced gene expression, anaerobic metabolism, angiogenesis, tissue remodeling, cell-cell contact, high-throughput screening, anti-metastatic agents
- MeSH terms
- Animals, Humans, Neoplasm Metastasis, Neoplasm Proteins, Neoplasms, Signal Transduction, Cell Hypoxia, Gene Expression Regulation, Neoplastic, Disease Progression
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