biostudies-literatureBalamurugan KCCR NIH HHSIntramural NIH HHSNCI NIH HHS4106-17https://www.ebi.ac.uk/biostudies/studies/S-EPMC3018791biostudies-literatureUnknown29(24)Inflammation and hypoxia are known to promote the metastatic progression of tumours. The CCAAT/enhancer-binding protein-δ (C/EBPδ, CEBPD) is an inflammatory response gene and candidate tumour suppressor, but its physiological role in tumourigenesis in vivo is unknown. Here, we demonstrate a tumour suppressor function of C/EBPδ using transgenic mice overexpressing the Neu/Her2/ERBB2 proto-oncogene in the mammary gland. Unexpectedly, this study also revealed that C/EBPδ is necessary for efficient tumour metastasis. We show that C/EBPδ is induced by hypoxia in tumours in vivo and in breast tumour cells in vitro, and that C/EBPδ-deficient cells exhibit reduced glycolytic metabolism and cell viability under hypoxia. C/EBPδ supports CXCR4 expression. On the other hand, C/EBPδ directly inhibits eThe EMBO journalThe tumour suppressor C/EBPδ inhibits FBXW7 expression and promotes mammary tumour metastasis.PMC3018791HHSN261200800001EHHSN261200800001CSterneck EWang JMLeighty RSharan STsai HHBalamurugan KAnver MfalseThe tumour suppressor C/EBPδ inhibits FBXW7 expression and promotes mammary tumour metastasis.Inflammation and hypoxia are known to promote the metastatic progression of tumours. The CCAAT/enhancer-binding protein-δ (C/EBPδ, CEBPD) is an inflammatory response gene and candidate tumour suppressor, but its physiological role in tumourigenesis in vivo is unknown. Here, we demonstrate a tumour suppressor function of C/EBPδ using transgenic mice overexpressing the Neu/Her2/ERBB2 proto-oncogene in the mammary gland. Unexpectedly, this study also revealed that C/EBPδ is necessary for efficient tumour metastasis. We show that C/EBPδ is induced by hypoxia in tumours in vivo and in breast tumour cells in vitro, and that C/EBPδ-deficient cells exhibit reduced glycolytic metabolism and cell viability under hypoxia. C/EBPδ supports CXCR4 expression. On the other hand, C/EBPδ directly inhibits e2010-01-01T00:00:00Z2010 Dec2025-04-26T05:09:07.032Z2019-03-27T00:37:59ZS-EPMC30187912107639210.1038/emboj.2010.280