Cited by 339Cancer, Hypoxia, and MetabolismAngiogenesis and VEGF in CancerMechanisms of cancer metastasis

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Hypoxia-Inducible Factor-1α Is a Key Regulator of Metastasis in a Transgenic Model of Cancer Initiation and Progression

Liao, Debbie, Corle, Courtney, Seagroves, Tiffany N., Johnson, Randall S.·2007·Cancer Research

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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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Crossref · 10.1158/0008-5472.can-06-2701

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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
ORCID: Liao, Debbie
Seagroves, Tiffany N.
Johnson, Randall S.
Venue: Cancer Research
Publisher: American Association for Cancer Research (AACR)
Published: 2007-01-15
Volume: 67
Issue: 2
Pages: 563-572
ISSN: 0008-5472 (ISSN-L)
1538-7445
DOI: 10.1158/0008-5472.can-06-2701
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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Hypoxia-Inducible Factor-1α Is a Key Regulator of Metastasis in a Transgenic Model of Cancer Initiation and Progression

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