PMID- 21076392
OWN - NLM
STAT- MEDLINE
DCOM- 20110113
LR  - 20211020
IS  - 1460-2075 (Electronic)
IS  - 0261-4189 (Print)
IS  - 0261-4189 (Linking)
VI  - 29
IP  - 24
DP  - 2010 Dec 15
TI  - The tumour suppressor C/EBPdelta inhibits FBXW7 expression and promotes mammary 
      tumour metastasis.
PG  - 4106-17
LID - 10.1038/emboj.2010.280 [doi]
AB  - Inflammation and hypoxia are known to promote the metastatic progression of 
      tumours. The CCAAT/enhancer-binding protein-delta (C/EBPdelta, 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/EBPdelta using transgenic mice overexpressing the Neu/Her2/ERBB2 
      proto-oncogene in the mammary gland. Unexpectedly, this study also revealed that 
      C/EBPdelta is necessary for efficient tumour metastasis. We show that C/EBPdelta is 
      induced by hypoxia in tumours in vivo and in breast tumour cells in vitro, and 
      that C/EBPdelta-deficient cells exhibit reduced glycolytic metabolism and cell 
      viability under hypoxia. C/EBPdelta supports CXCR4 expression. On the other hand, 
      C/EBPdelta directly inhibits expression of the tumour suppressor F-box and WD 
      repeat-domain containing 7 gene (FBXW7, FBW7, AGO, Cdc4), encoding an F-box 
      protein that promotes degradation of the mammalian target of rapamycin (mTOR). 
      Consequently, C/EBPdelta enhances mTOR/AKT/S6K1 signalling and augments translation 
      and activity of hypoxia-inducible factor-1alpha (HIF-1alpha), which is necessary for 
      hypoxia adaptation. This work provides new insight into the mechanisms by which 
      metastasis-promoting signals are induced specifically under hypoxia.
FAU - Balamurugan, Kuppusamy
AU  - Balamurugan K
AD  - Laboratory of Cell and Developmental Signalling, CCR, National Cancer Institute, 
      Frederick, MD 21702, USA.
FAU - Wang, Ju-Ming
AU  - Wang JM
FAU - Tsai, Hsin-Hwa
AU  - Tsai HH
FAU - Sharan, Shikha
AU  - Sharan S
FAU - Anver, Miriam
AU  - Anver M
FAU - Leighty, Robert
AU  - Leighty R
FAU - Sterneck, Esta
AU  - Sterneck E
LA  - eng
GR  - HHSN261200800001C/RC/CCR NIH HHS/United States
GR  - HHSN261200800001E/CA/NCI NIH HHS/United States
GR  - ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20101112
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (F-Box Proteins)
RN  - 0 (F-Box-WD Repeat-Containing Protein 7)
RN  - 0 (Fbxw7 protein, mouse)
RN  - 142662-43-9 (CCAAT-Enhancer-Binding Protein-delta)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
SB  - IM
CIN - EMBO J. 2010 Dec 15;29(24):4063-5. PMID: 21157479
MH  - Animals
MH  - CCAAT-Enhancer-Binding Protein-delta/*metabolism
MH  - Cell Proliferation
MH  - Cell Survival
MH  - Cells, Cultured
MH  - F-Box Proteins/*biosynthesis
MH  - F-Box-WD Repeat-Containing Protein 7
MH  - *Gene Expression Regulation
MH  - Glycolysis
MH  - *Hypoxia
MH  - Mammary Neoplasms, Animal/pathology/physiopathology/*secondary
MH  - Mice
MH  - Mice, Transgenic
MH  - Neoplasm Metastasis/*pathology/physiopathology
MH  - Ubiquitin-Protein Ligases/*biosynthesis
PMC - PMC3018791
COIS- The authors declare that they have no conflict of interest.
EDAT- 2010/11/16 06:00
MHDA- 2011/01/14 06:00
PMCR- 2011/12/15
CRDT- 2010/11/16 06:00
PHST- 2010/04/14 00:00 [received]
PHST- 2010/10/20 00:00 [accepted]
PHST- 2010/11/16 06:00 [entrez]
PHST- 2010/11/16 06:00 [pubmed]
PHST- 2011/01/14 06:00 [medline]
PHST- 2011/12/15 00:00 [pmc-release]
AID - emboj2010280 [pii]
AID - 10.1038/emboj.2010.280 [doi]
PST - ppublish
SO  - EMBO J. 2010 Dec 15;29(24):4106-17. doi: 10.1038/emboj.2010.280. Epub 2010 Nov 
      12.