Cited by 71Cancer, Hypoxia, and MetabolismCancer Cells and MetastasisAngiogenesis and VEGF in Cancer

Hypoxia-inducible factors promote breast cancer stem cell specification and maintenance in response to hypoxia or cytotoxic chemotherapy

Lisha Xiang, Gregg L. Semenza·2019·Advances in Cancer Research

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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Registry

Crossref · 10.1016/bs.acr.2018.11.001

Cites

252 of 252 references verified0 citation errors · 0 not checkable

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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).”

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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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