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PMID: 24156323 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Role of hypoxia-inducible factors in breast cancer metastasis.

Future oncology (London, England) ·Vol. 9 ·No. 11 ·2013-11-00 ·Pages 1623-36

Gilkes DM, Semenza GL

Abstract

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.

MeSH Terms
Animals Antineoplastic Agents/pharmacology,therapeutic use Basic Helix-Loop-Helix Transcription Factors/antagonists & inhibitors,physiology Breast Neoplasms/drug therapy,metabolism,pathology Cell Movement Cell Survival Epithelial-Mesenchymal Transition Female Humans Hypoxia-Inducible Factor 1/antagonists & inhibitors,physiology Lymphatic Metastasis Neoplasm Invasiveness Tumor Microenvironment
Chemicals
Antineoplastic Agents Basic Helix-Loop-Helix Transcription Factors Hypoxia-Inducible Factor 1 endothelial PAS domain-containing protein 1
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Gilkes Daniele M
Vascular Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Semenza Gregg L
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Article Info
Journal
Future oncology (London, England)
Abbr.
Future Oncol
ISSN
1744-8301
DOI
10.2217/fon.13.92
Published
2013-11-00
Pages
1623-36
Language
English
Region
England
NLM ID
101256629
PMCID
PMC4659402
Subset
IM
Grants
NCI NIH HHS · P30 CA006973 · United States
NCI NIH HHS · U54 CA143868 · United States
NCI NIH HHS · U54-CA143868 · United States
External Links
PubMed source DOI: 10.2217/fon.13.92 PMC Full Text View journal details
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