Neuregulin 1-HER axis as a key mediator of hyperglycemic memory effects in breast cancer

Touchstone Diabetes Center and Departments of Internal Medicine, Pathology, Surgery, Pharmacology, and Cell Biology, Simmons Cancer Center, and McDermott Center for Human Growth and Development and Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 12/2012; 109(51). DOI: 10.1073/pnas.1214400109
Source: PubMed


Poor outcomes in diabetic patients are observed across a range of human tumors, suggesting that cancer cells develop unique characteristics under diabetic conditions. Cancer cells exposed to hyperglycemic insults acquire permanent aggressive traits of tumor growth, even after a return to euglycemic conditions. Comparative genome-wide mapping of hyperglycemia-specific open chromatin regions and concomitant mRNA expression profiling revealed that the neuregulin-1 gene, encoding an established endogenous ligand for the HER3 receptor, is activated through a putative distal enhancer. Our findings highlight the targeted inhibition of NRG1-HER3 pathways as a potential target for the treatment breast cancer patients with associated diabetes.

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