title: Neuregulin 1-HER axis as a key mediator of hyperglycemic memory effects in breast cancer.
abstract: 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.
authors.affiliation: Touchstone Diabetes Center and Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Park
authors.forename: Venetia R
authors.initials: VR
authors.lastname: Sarode
authors.forename: David
authors.initials: D
authors.lastname: Euhus
authors.forename: Ralf
authors.initials: R
authors.lastname: Kittler
authors.forename: Philipp E
authors.initials: PE
authors.lastname: Scherer
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000150:complications / Q000378:metabolism; D016466:CHO Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006224:Cricetinae; D003920:Diabetes Mellitus / Q000378:metabolism*; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D018392:Genomic Imprinting; D057809:HEK293 Cells; D006801:Humans; D006943:Hyperglycemia / Q000150:complications / Q000378:metabolism; D051379:Mice; D020890:Neuregulin-1 / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D020893:Receptor, ErbB-3 / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D020890:Neuregulin-1; D012333:RNA, Messenger; D020893:Receptor, ErbB-3