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Cited by 42Cancer, Hypoxia, and MetabolismMechanisms of cancer metastasisCancer Cells and Metastasis

Hypoxia‑inducible factor 1 mediates intermittent hypoxia‑induced migration of human breast cancer MDA‑MB‑231 cells

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Liu, Litao, Liu, Wenlan, Wang, Lili, Zhu, Ting, Zhong, Jianhua, Xie, Ni·2017·Oncology Letters
DOI 10.3892/ol.2017.7223PMC PMC5727604
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Abstract

Metastasis is the major cause of triple-negative breast cancer (TNBC)-associated mortality. Hypoxia promotes cancer cell migration and remote metastasis, which occur with hypoxia inducible factor 1α (HIF-1α) stabilization and vimentin upregulation. However, the evolutionary dynamics that link the changes in HIF-1α and vimentin levels under hypoxic conditions are not well understood. In the present study, the effects of intermittent hypoxia (IH), continuous hypoxia (CH) and normoxia on the migration and proliferation of human TNBC MDA-MB-231 cells were investigated. The results demonstrated that IH significantly increased the migration of MDA-MB-231 cells, and this effect was dependent on the number of cycles of hypoxia-reoxygenation. Unexpectedly, IH significantly inhibited cell proliferation, while CH only caused such an effect if hypoxia extended for ≥3 days. IH and CH induced HIF-1α protein accumulation and vimentin upregulation, with a greater effect observed in IH. Knockdown of HIF-1α with siRNA abolished IH-induced cell migration and vimentin upregulation. In summary, multiple cycles of hypoxia and reoxygenation have a more pronounced effect on the promotion of TNBC invasiveness than CH; HIF-1α activation and downstream vimentin upregulation may account for this phenotypic change.

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  • Cyclical intermittent hypoxia may increase expression of genes associated with metastases and cancer cell migration.

    “Lastly, CIH may increase expression of genes associated with metastases,881 and cancer cell migration.882”

    From International Consensus Statement on Obstructive Sleep Apnea (2023) · cites this paper as [882]

  • In vitro models have shown that cyclical intermittent hypoxia produces molecular changes that promote cancer progression or metastases.

    “(2) CIH results in molecular changes that promote cancer progression or metastases.”

    From International Consensus Statement on Obstructive Sleep Apnea (2023) · cites this paper as [882]

  • In vitro models have shown that cyclical intermittent hypoxia produces changes distinct from sustained hypoxia.

    “In vitro models have provided two main findings: (1) CIH results in changes that are distinct from sustained hypoxia;”

    From International Consensus Statement on Obstructive Sleep Apnea (2023) · cites this paper as [882]

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Cited by

Sorted by citations

Authors
Liu, L., Liu, W., Wang, L., Zhu, T., Zhong, J., & Xie, N.
Affiliations
Shenzhen Second People's Hospital (CN)
Corresponding author
Xie, Ni
ORCID
Venue
Oncology Letters
Publisher
Spandidos Publications
Published
2017-10-19
Volume
14
Issue
6
Pages
7715-7722
ISSN
  • 1792-1074 (ISSN-L)
  • 1792-1082
DOI
10.3892/ol.2017.7223
PMC
PMC5727604
OpenAlex
W2766696823
Cited by
42
References
1
Citations by year
2026: 1 · 2025: 3 · 2024: 2 · 2023: 6 · 2022: 5 · 2021: 2 · 2020: 9 · 2019: 6 · 2018: 8
FWCI
2.11
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Oncology Letters (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
Natural Science Foundation of Guangdong Province (2016A030313029)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Keywords
hypoxia-inducible factor-1α, intermittent hypoxia, triple-negative breast cancer, MDA-MB-231 cells, cell migration, vimentin, hypoxia/reoxygenation, cell proliferation, metastasis, tumor invasion

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