ArticleThe Journal of biological chemistry2011
Endogenous myoglobin in breast cancer is hypoxia-inducible by alternative transcription and functions to impair mitochondrial activity: a role in tumor suppression?
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 52 citations in OpenAlex.
- Role of Endogenous Myoglobin in Anthracycline Response in Breast Cancer.Biomolecules · 2026Article
- Myoglobin inhibits breast cancer cell fatty acid oxidation and migration via heme-dependent oxidant production and not fatty acid binding.Free radical biology & medicine · 2024Article
- Review
- Endogenous myoglobin expression in mouse models of mammary carcinoma reduces hypoxia and metastasis in PyMT mice.Scientific reports · 2023Article
- Transcriptomic Profile of Canine Mammary Ductal Carcinoma.International journal of molecular sciences · 2023Article
- Pro-Apoptotic and Anti-Invasive Properties Underscore the Tumor-Suppressing Impact of Myoglobin on a Subset of Human Breast Cancer Cells.International journal of molecular sciences · 2022Article
- Myoglobin expression by alternative transcript in different mesenchymal stem cells compartments.Stem cell research & therapy · 2022Article
- Myoglobin regulates fatty acid trafficking and lipid metabolism in mammary epithelial cells.PloS one · 2022Article
- Hypoxic and nitrosative stress conditions modulate expression of myoglobin genes in a carcinogenic hepatobiliary trematode, Clonorchis sinensis.PLoS neglected tropical diseases · 2021Article
- Targeting neovascularization and respiration of tumor grafts grown on chick embryo chorioallantoic membranes.PloS one · 2021Article
- Myoglobin Protects Breast Cancer Cells Due to Its ROS and NO Scavenging Properties.Frontiers in endocrinology · 2021Article
- Expression of Myoglobin in Normal and Cancer Brain Tissues: Correlation With Hypoxia Markers.Frontiers in oncology · 2021Article
- Myoglobin promotes nitrite-dependent mitochondrial S-nitrosation to mediate cytoprotection after hypoxia/reoxygenation.Nitric oxide : biology and chemistry · 2020Article
- Lessons from the post-genomic era: Globin diversity beyond oxygen binding and transport.Redox biology · 2020Review
- Targeted Myoglobin Delivery as a Strategy for Enhancing the Sensitivity of Hypoxic Cancer Cells to Radiation.iScience · 2020Article
- The role of myoglobin in epithelial cancers: Insights from transcriptomics.International journal of molecular medicine · 2020Article
- Myoglobin induces mitochondrial fusion, thereby inhibiting breast cancer cell proliferation.The Journal of biological chemistry · 2019Article
- Influence of hypoxia-related genetic polymorphisms on the prognosis of patients with metastatic gastric cancer treated with EOF.Oncology letters · 2018Article
- Integration of RNA-Seq data with heterogeneous microarray data for breast cancer profiling.BMC bioinformatics · 2017Article
- ITIH5 mediates epigenetic reprogramming of breast cancer cells.Molecular cancer · 2017Article
Corrections and comments
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Authors and funding
20 authors at 9 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recently, immunohistochemical analysis of myoglobin (MB) in human breast cancer specimens has revealed a surprisingly widespread expression of MB in this nonmuscle context. The positive correlation with hypoxia-inducible factor 2α (HIF-2α) and carbonic anhydrase IX suggested that oxygen regulates myoglobin expression in breast carcinomas. Here, we report that MB mRNA and protein levels are robustly induced by prolonged hypoxia in breast cancer cell lines, in part via HIF-1/2-dependent transactivation. The hypoxia-induced MB mRNA originated from a novel alternative transcription start site 6 kb upstream of the ATG codon. MB regulation in normal and tumor tissue may thus be fundamentally different. Functionally, the knockdown of MB in MDA-MB468 breast cancer cells resulted in an unexpected increase of O(2) uptake and elevated activities of mitochondrial enzymes during hypoxia. Silencing of MB transcription attenuated proliferation rates and motility capacities of hypoxic cancer cells and, surprisingly, also fully oxygenated breast cancer cells. Endogenous MB in cancer cells is apparently involved in controlling oxidative cell energy metabolism, contrary to earlier findings on mouse heart, where the targeted disruption of the Mb gene did not effect myocardial energetics and O(2) consumption. This control function of MB seemingly impacts mitochondria and influences cell proliferation and motility, but it does so in ways not directly related to the facilitated diffusion or storage of O(2). Hypothetically, the mitochondrion-impairing role of MB in hypoxic cancer cells is part of a novel tumor-suppressive function.
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