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Cited by 14Cancer, Hypoxia, and MetabolismCancer Cells and MetastasisCell death mechanisms and regulation

Surviving without oxygen: Hypoxia regulation of mammary morphogenesis and anoikis

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Whelan, Kelly A., Reginato, Mauricio J.·2011·Cell Cycle
DOI 10.4161/cc.10.14.16532
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Abstract

Tumor hypoxia correlates with resistance to chemotherapy, increased incidence of metastasis and poor clinical prognosis. Early breast cancer lesions, such as carcinoma in situ, characterized by filled lumens, are often associated with hypoxic markers. However, the contribution of hypoxia to changes in tissue architecture in early pre-malignant lesions is not well defined. Using three-dimensional basement membrane cultures of mammary epithelial cells, we recently reported that acini-like structures exposed to hypoxia display epithelial disorganization and delayed lumen formation. We found that hypoxia, via HIF-1α, targets signaling pathways, specifically the Erk-Bim axis, to suppress anoikis-cell death in a 3D acinar model. Here, we discuss these findings further and present additional data, indicating that hypoxia-mediated alterations in acinar architecture and anoikis-associated Erk-Bim signaling are maintained in mammary epithelial cells after reoxygenation. Taken together, these findings may offer new insight into the contribution of hypoxia-mediated signaling in the progression of early breast cancer lesions and possible treatment of hypoxic cancers.

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  • Multiple research results have shown that autophagy protects cells exposed to various forms of stress, including nutrient deprivation, growth factor regression, endoplasmic reticulum stress, and ischemia.

    “In addition, multiple research results have shown that autophagy protects cells exposed to various forms of stress, including nutrient deprivation, growth factor regression, endoplasmic reticulum stress, and ischemia.[23–25]”

    From Autophagy, not apoptosis, plays a role in lumen formation of eccrine gland organoids (2022) · cites this paper as [24]

    The “Targeting Anoikis-Resistant Hypoxic Cancer Cells” section describes autophagy as a survival mechanism under stress and says it promotes survival during loss of adhesion and prevents cell death during cycling hypoxia. It does not establish the claimed protection during nutrient deprivation, growth-factor regression, endoplasmic reticulum stress, or ischemia. (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
Whelan, K. A., & Reginato, M. J.
Affiliations
Drexel University (US)
Corresponding author
Reginato, Mauricio J.
ORCID
Venue
Cell Cycle
Publisher
Informa UK Limited
Published
2011-07-15
Volume
10
Issue
14
Pages
2287-2294
ISSN
  • 1538-4101 (ISSN-L)
  • 1551-4005
DOI
10.4161/cc.10.14.16532
OpenAlex
W2047399966
Cited by
14
References
0
Citations by year
2025: 1 · 2022: 1 · 2020: 2 · 2018: 1 · 2016: 1 · 2014: 5 · 2013: 1 · 2012: 2
FWCI
0.87
Type
journal article
Language
en
Open access
Locations
  • Cell Cycle (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • U.S. Department of Defense
  • Drexel University
  • College of Medicine, Drexel University
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 › Cell death mechanisms and regulation
Keywords
tumor hypoxia, mammary gland morphogenesis, anoikis, HIF-1α, mammary acini, lumen formation, mammary epithelial cells, carcinoma in situ, reoxygenation, early breast cancer
MeSH terms
Bcl-2-Like Protein 11, Breast Neoplasms, Epithelial Cells, Female, Humans, Membrane Proteins, Oxygen, Proto-Oncogene Proteins, Signal Transduction, Cell Hypoxia, Anoikis, Mammary Glands, Human, Extracellular Signal-Regulated MAP Kinases, Apoptosis Regulatory Proteins, Hypoxia-Inducible Factor 1, alpha Subunit

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