Hypoxia-Inducible Factor-1α Is a Key Regulator of Metastasis in a Transgenic Model of Cancer Initiation and Progression
Abstract
Adaptation to hypoxia is a critical step in tumor progression and is, in part, regulated by the transcription factor hypoxia-inducible factor-1α (HIF-1α). Xenograft models have been extensively used to characterize the role of HIF-1α in experimental cancers. Although these models provide an understanding of tumor growth at terminal stages of malignancy, they do not address tumor initiation or metastatic progression. To elucidate these roles, HIF-1α was conditionally deleted in the mammary epithelium of a transgenic mouse model for metastatic breast cancer. Conditional deletion of HIF-1α in the mammary epithelium resulted in delayed tumor onset and retarded tumor growth; this was correlated with decreased tumor cell proliferation. Tumors with conditional deletion of HIF-1α were also less vascular during early tumor progression. Perhaps most surprisingly, deletion of HIF-1α in the mammary epithelium resulted in decreased pulmonary metastasis. These results show that whereas HIF-1α is not required for the initiation of breast tumor growth or tumor cell metastasis, the transcriptional activity of HIF-1α is a significant positive regulator of tumor progression and metastatic potential. [Cancer Res 2007;67(2):563–72]
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Insights from a transgenic mouse model of metastatic breast cancer and xenograft models of breast cancer point to HIF-1α as a critical regulator of metastasis.
“Insights from a transgenic mouse model of metastatic breast cancer (Liao et al., 2007) and xenograft models of breast cancer (Hiraga et al., 2007;Lu et al., 2010) also point to HIF-1α as a critical regulator of metastasis.”
From Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer (2016) · cites this paper as Liao et al., 2007
Inactivation of HIF decreases the metastatic potential of tumor cells.
“whereas inactivation of HIF decreases the metastatic potential of tumor cells”
From Hypoxic control of metastasis (2016) · cites this paper as [46]
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- Authors
- Liao, D., Corle, C., Seagroves, T. N., & Johnson, R. S.
- Affiliations
- University of California San Diego (US)
- 1Division of Biological Sciences, Molecular Biology Section, and
- Venue
- Cancer Research
- Published
- 2007-01-15
- Volume
- 67
- Issue
- 2
- Pages
- 563-572
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2167510293
- Cited by
- 339
- References
- 38
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 5 · 2023: 9 · 2022: 17 · 2021: 20 · 2020: 13 · 2019: 14 · 2018: 14 · 2017: 14 · 2016: 17 · 2015: 26 · 2014: 21 · 2013: 25 · 2012: 29
- FWCI
- 10.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (R01CA082515, CA 082515)
- 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 › Molecular Biology › Mechanisms of cancer metastasis
- Keywords
- hypoxia-inducible factor-1α, metastasis, breast cancer, tumor initiation, tumor progression, mammary epithelium, conditional gene deletion, transgenic mouse model, tumor hypoxia, tumor cell proliferation, tumor vascularization, lung metastasis
- MeSH terms
- Animals, Female, Hyperplasia, Lung Neoplasms, Male, Mammary Neoplasms, Experimental, Mice, Transgenic, Neoplasm Metastasis, Transcription, Genetic, Mammary Neoplasms, Animal, Mice, Knockout, Disease Progression, Cell Growth Processes, Mice, Hypoxia-Inducible Factor 1, alpha Subunit
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