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Hypoxia-inducible factors promote breast cancer stem cell specification and maintenance in response to hypoxia or cytotoxic chemotherapy
Abstract
Clinical studies have revealed that breast cancers contain regions of intratumoral hypoxia (reduced oxygen availability), which activates hypoxia-inducible factors (HIFs). The relationship between intratumoral hypoxia, distant metastasis and cancer mortality has been well established. A major mechanism by which intratumoral hypoxia contributes to disease progression is through induction of the breast cancer stem cell (BCSC) phenotype. BCSCs are a small subpopulation of cells with the capability for self-renewal. BCSCs have been implicated in resistance to chemotherapy, disease recurrence, and metastasis. In this review, we will discuss our current understanding of the molecular mechanisms underlying HIF-dependent induction of the BCSC phenotype in response to hypoxia or chemotherapy.
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“Hypoxia-inducible factors (HIFs) play critical roles in cancer progression by activating the transcription of a large battery of genes encoding proteins that play key roles in angiogenesis, glucose metabolism, invasion/metastasis, stem cell specification, protumoral inflammatory responses, and tumor immune evasion (18, 23–27).”
From HIF inhibitor 32-134D eradicates murine hepatocellular carcinoma in combination with anti-PD1 therapy (2022) · cites this paper as [27]
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Cabello, C. M., Bair, W. B., & Wondrak, G. T. (2007) · PubMed · Cited by 110
Snail1 induces epithelial-to-mesenchymal transition and tumor initiating stem cell characteristics
Dang, H. T., Ding, W., Emerson, D., & Rountree, C. B. (2011) · BMC Cancer · doi:10.1186/1471-2407-11-396 · Cited by 106
Krutilina, R. I., Sun, W., Sethuraman, A., Brown, M., Seagroves, T. N., Pfeffer, L. M., Ignatova, T. N., & Fan, M. (2014) · Breast Cancer Research · doi:10.1186/bcr3693 · Cited by 106
WW domain-mediated interaction with Wbp2 is important for the oncogenic property of TAZ
Chan, S. W., Lim, C. J., Huang, C.-J., Chong, Y. F., Gunaratne, H. J., Hogue, K. A., Blackstock, W. P., Harvey, K. F., & Hong, W. (2010) · Oncogene · doi:10.1038/onc.2010.438 · Cited by 104
Comprehensive Genome Sequence Analysis of a Breast Cancer AmpliconPreprint
Collins, C. C., Volik, S. V., Kowbel, D., Ginzinger, D. G., Ylstra, B., Cloutier, T., Hawkins, T. L., Predki, P. F., Martin, C., Wernick, M., et al. (2001) · Genome Research · doi:10.1101/gr.gr1743r · Cited by 104
Flagged first, then by citations
4 of the 256 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Hypoxia-inducible factors: cancer progression and clinical translation
Wicks, E. E., & Semenza, G. L. (2022) · Journal of Clinical Investigation · doi:10.1172/jci159839 · Cited by 626
Self-citationHIFs, angiogenesis, and metabolism: Elusive enemies in breast cancer
de Heer, E. C., Jalving, M., & Harris, A. L. (2020) · Journal of Clinical Investigation · doi:10.1172/jci137552 · Cited by 372
Bai, R., Li, Y., Jian, L., Yue-hui, Y., Zhao, L., & Wei, M. (2022) · Molecular Cancer · doi:10.1186/s12943-022-01645-2 · Cited by 296
The role of hypoxia‐inducible factor 1 in tumor immune evasion
Li, Y., Wu, W., Wang, X., Fang, L., Adam, V., Nepovimová, E., Wu, Q., & Kuča, K. (2020) · Medicinal Research Reviews · doi:10.1002/med.21771 · Cited by 276
Targeting Breast Cancer Stem Cells
Zhang, L., Chen, W., Liu, S., & Chen, C. (2023) · International Journal of Biological Sciences · doi:10.7150/ijbs.76187 · Cited by 196
Metadata
- Authors
- Xiang, L., & Semenza, G. L.
- Affiliations
- Sichuan University (CN)
- Johns Hopkins University (US)
- Corresponding author
- Gregg L. Semenza
- Venue
- Advances in Cancer Research
- Publisher
- Elsevier
- Published
- 2019
- Volume
- 141
- Pages
- 175-212
- ISSN
- 0065-230X (ISSN-L)
- OpenAlex
- W2904539422
- Cited by
- 71
- References
- 256
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 10 · 2023: 8 · 2022: 12 · 2021: 14 · 2020: 12 · 2019: 5
- FWCI
- 9.82
- Type
- book chapter
- Language
- en
- Open access
- closed
- Locations
- Advances in cancer research (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 › Angiogenesis and VEGF in Cancer
- Keywords
- hypoxia-inducible factor, breast cancer stem cells, intratumoral hypoxia, chemoresistance, self-renewal, metastasis, recurrence, HIF signaling
- MeSH terms
- Animals, Breast Neoplasms, Female, Humans, Neoplastic Stem Cells, Cell Hypoxia, Cell Line, Tumor, Hypoxia-Inducible Factor 1, alpha Subunit
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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