The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
O-GlcNAcylation Regulates Cancer Metabolism and Survival Stress Signaling via Regulation of the HIF-1 Pathway
Open accessAbstract
The Hexosamine Biosynthetic Pathway leads to elevated post-translation addition of O-linked-βN-acetylglucosamine (O-GlcNAc) on intracellular proteins. Cancer cells elevate total O-GlcNAcylation by increasing O-GlcNAc transferase (OGT) and/or decreasing O-GlcNAcase (OGA) levels. Reducing O-GlcNAcylation in cancer cells inhibits oncogenesis. Here, we demonstrate that O-GlcNAcylation regulates glycolysis in cancer cells via HIF-1α and its transcriptional target GLUT1. Reducing O-GlcNAcylation increases α-ketoglutarate, HIF-1 hydroxylation and interaction with VHL resulting in HIF-1α degradation. Reducing O-GlcNAcylation in cancer cells results in activation of ER stress and apoptosis of cancer cells mediated through CHOP induction of BCL2-family proteins. HIF-1α and GLUT1 are critical for OGT-mediated regulation of metabolic stress as overexpression of stable HIF-1 or GLUT1 rescues metabolic defects and apoptosis. Human basal-like breast cancers with high levels of HIF-1α contain elevated OGT, O-GlcNAcylation and lower OGA levels correlate independently with poor patient outcome. Thus, O-GlcNAcylation regulates cancer cell metabolic reprograming and survival stress signaling via regulation of HIF-1α.
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Cites
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A Small Molecule That Inhibits OGT Activity in Cells
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Iron and the pathophysiology of diabetes
Harrison, A. V., Lorenzo, F. R., & McClain, D. A. (2023) · Annual Review of Physiology · doi:10.1146/annurev-physiol-022522-102832 · Cited by 161
Hypoxia-induced switch in SNAT2/SLC38A2 regulation generates endocrine resistance in breast cancer
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Metadata
- Authors
- Ferrer, C. M., Lynch, T. P., Sodi, V. L., Falcone, J. N., Schwab, L. P., Peacock, D. L., Vocadlo, D. J., Seagroves, T. N., & Reginato, M. J.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2014-06
- Volume
- 54
- Issue
- 5
- Pages
- 820-831
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2018024152
- Cited by
- 442
- References
- 8
- FWCI
- 8.65
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Ferrer, C. M., Lynch, T. P., Sodi, V. L., Falcone, J. N., Schwab, L. P., Peacock, D. L., Vocadlo, D. J., Seagroves, T. N., & Reginato, M. J. (2014). O-GlcNAcylation Regulates Cancer Metabolism and Survival Stress Signaling via Regulation of the HIF-1 Pathway. Molecular Cell. https://doi.org/10.1016/j.molcel.2014.04.026
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