The DOI matches its Crossref record; 126 of the 126 references it cites were found in a registry or an index.
Role of Hypoxia-Inducible Factors in Breast Cancer Metastasis
Open accessAbstract
Human breast tumors contain regions of hypoxia in which cells that are located far from a functional blood vessel have significantly reduced oxygen concentrations when compared with normal mammary tissue. Breast cancer cells adapt to hypoxic conditions by increasing levels of hypoxia-inducible factors (HIFs), which induce the expression of multiple genes involved in angiogenesis, glucose utilization, resistance to oxidative stress, cell proliferation, resistance to apoptosis, invasion and metastasis. Breast cancer patients with increased HIF expression levels in primary tumor biopsies are at increased risk of metastasis. This is an important finding since 90% of breast cancer deaths are the result of metastasis, primarily to the bone, lungs, liver, brain and regional lymph nodes. Although the prognostic significance of reduced oxygen levels in primary breast tumors of cancer patients is well recognized, the mechanisms underlying hypoxia-induced, HIF-dependent breast cancer metastasis are just beginning to be uncovered. Recent studies have implicated HIF target genes in every step of the metastatic process. Drugs, such as digoxin, show the potential therapeutic effects of blocking HIF activity by decreasing primary tumor growth, vascularization, invasion and metastasis in animal models of breast cancer.
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“In breast cancer, HIF-1α acts as a master regulator for the expression of genes that promote tumor growth, vascularization, and metastasis4.”
From Liposomal Formulation of HIF-1α Inhibitor Echinomycin Eliminates Established Metastases of Triple-negative Breast Cancer (2020) · cites this paper as [4]
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7 retracted
Lysyl oxidase is essential for hypoxia-induced metastasis
Erler, J. T., Bennewith, K. L., Nicolau, M., Dornhöfer, N., Kong, C., Le, Q.-T., Chi, J.-T. A., Jeffrey, S. S., & Giaccia, A. J. (2006) · Nature · doi:10.1038/nature04695 · Cited by 1,309
RetractedGilkes, D. M., Bajpai, S. K., Chaturvedi, P., Wirtz, D., & Semenza, G. L. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.442939 · Cited by 473
Self-citationRetractedRETRACTED: Acriflavine inhibits HIF-1 dimerization, tumor growth, and vascularization
Lee, K., Zhang, H., Qian, D. Z., Rey, S., Liu, J. O., & Semenza, G. L. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909353106 · Cited by 451
Self-citationRetractedZhang, H., Wong, C. C. L., Wei, H., Gilkes, D. M., Korangath, P., Chaturvedi, P., Schito, L., Chen, J., Krishnamachary, B., Winnard, P. T., et al. (2012) · Oncogene · doi:10.1038/onc.2011.365 · Cited by 326
Self-citationRetractedRETRACTED: Collagen Prolyl Hydroxylases Are Essential for Breast Cancer Metastasis
Gilkes, D. M., Chaturvedi, P., Bajpai, S., Wong, C. C., Wei, H., Pitcairn, S., Hubbi, M. E., Wirtz, D., & Semenza, G. L. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-3963 · Cited by 296
Self-citationRetractedLee, K., Qian, D. Z., Rey, S., Wei, H., Liu, J. O., & Semenza, G. L. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812801106 · Cited by 289
Self-citationRetractedProcollagen lysyl hydroxylase 2 is essential for hypoxia-induced breast cancer metastasis
Gilkes, D. M., Bajpai, S., Wong, C. C., Chaturvedi, P., Hubbi, M. E., Wirtz, D., & Semenza, G. L. (2013) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-12-0629 · Cited by 252
Self-citationRetractedMolecular portraits of human breast tumours
Perou, C., Sørlie, T., Eisen, M., van de Rijn, M., Jeffrey, S., Rees, C. A., Pollack, J., Ross, D., Johnsen, H., Akslen, L., et al. (2000) · Nature · doi:10.1038/35021093 · Cited by 16,551
Comprehensive molecular portraits of human breast tumours
The Cancer Genome Atlas Network (2012) · Nature · doi:10.1038/nature11412 · Cited by 12,129
Targeting HIF-1 for cancer therapy
Semenza, G. L. (2003) · Nature Reviews Cancer · doi:10.1038/nrc1187 · Cited by 6,717 · cited 2×
“Clinically, this is supported by the finding that patients with primary tumors that have high HIF-1a levels have a greater likelihood of developing metastatic relapse and a shorter survival time [122].”
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NF-κB, inflammation, immunity and cancer: coming of age
Taniguchi, K., & Karin, M. (2018) · Nature Reviews Immunology · doi:10.1038/nri.2017.142 · Cited by 2,679
Hypoxia and the extracellular matrix: drivers of tumour metastasis
Gilkes, D. M., Semenza, G. L., & Wirtz, D. (2014) · Nature Reviews Cancer · doi:10.1038/nrc3726 · Cited by 1,520
Self-citationHypoxia-Inducible Factors: Master Regulators of Cancer Progression
Schito, L., & Semenza, G. L. (2016) · Trends in Cancer · doi:10.1016/j.trecan.2016.10.016 · Cited by 962
Self-citationMolecular landmarks of tumor hypoxia across cancer types
Bhandari, V., Hoey, C., Liu, L. Y., Lalonde, E., Ray, J., Livingstone, J., Lesurf, R., Shiah, Y.-J., Vujcic, T., Huang, X., et al. (2019) · Nature Genetics · doi:10.1038/s41588-018-0318-2 · Cited by 678
NF‐κB signaling in inflammation and cancer
Zhang, T., Ma, C., Zhang, Z., Zhang, H., & Hu, H. (2021) · MedComm · doi:10.1002/mco2.104 · Cited by 639
Metadata
- Authors
- Gilkes, D. M., & Semenza, G. L.
- Affiliations
- Johns Hopkins University (US)
- Venue
- Future Oncology
- Publisher
- Informa UK Limited
- Published
- 2013-10-24
- Volume
- 9
- Issue
- 11
- Pages
- 1623-1636
- ISSN
- 1479-6694 (ISSN-L)
- 1744-8301
- PMC
- PMC4659402
- OpenAlex
- W2126797928
- Cited by
- 274
- References
- 126
- Citations by year
- 2026: 2 · 2025: 17 · 2024: 20 · 2023: 22 · 2022: 24 · 2021: 40 · 2020: 26 · 2019: 29 · 2018: 25 · 2017: 22 · 2016: 15 · 2015: 17 · 2014: 12 · 2013: 1
- FWCI
- 1.24
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Future Oncology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (U54-CA143868)
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- hypoxia-inducible factor, breast cancer metastasis, tumor hypoxia, angiogenesis, glucose metabolism, oxidative stress resistance, apoptosis resistance, cell invasion, HIF target genes, prognostic factors, digoxin, HIF inhibitors, tumor vascularization
- MeSH terms
- Endothelial PAS Domain-Containing Protein 1, Animals, Antineoplastic Agents, Breast Neoplasms, Cell Movement, Cell Survival, Female, Humans, Lymphatic Metastasis, Neoplasm Invasiveness, Basic Helix-Loop-Helix Transcription Factors, Basic Helix-Loop-Helix Proteins, Hypoxia-Inducible Factor 1, Epithelial-Mesenchymal Transition, Tumor Microenvironment
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