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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HIFs play critical roles in cancer progression by activating transcription of genes encoding proteins involved in angiogenesis, glucose metabolism, invasion/metastasis, stem cell specification, protumoral inflammatory responses, and tumor immune evasion.
“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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- 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
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