PMID- 24501326
OWN - NLM
STAT- MEDLINE
DCOM- 20140624
LR  - 20161125
IS  - 1460-2180 (Electronic)
IS  - 0143-3334 (Linking)
VI  - 35
IP  - 5
DP  - 2014 May
TI  - Involvement of CDX2 in the cross talk between TNF-alpha and Wnt signaling pathway in 
      the colon cancer cell line Caco-2.
PG  - 1185-92
LID - 10.1093/carcin/bgu037 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha) is highly upregulated in inflammation and reduces 
      the expression of the intestinal transcription factor, Caudal-related homeobox 
      transcription factor 2 (CDX2). Wnt/beta-catenin signaling is critical for intestinal 
      cell proliferation, but a decreased CDX2 expression has influence on the Wnt 
      signaling-related genes and progression of colorectal cancer. Although several 
      inflammatory signaling pathways, including TNF-alpha, have been reported to promote 
      Wnt/beta-catenin activity and development of cancer, the underlying molecular 
      mechanisms remain unclear. The aim was to investigate the signaling pathways 
      involved in the TNF-alpha-mediated downregulation of CDX2, and its influence on 
      Wnt/beta-catenin signaling components in colon cancer cells. The expression of TNF-alpha 
      and CDX2 at the invasive front were evaluated by immunohistochemical staining and 
      showed reduced CDX2-positive cells in tumor buddings in areas with TNF-alpha 
      expression in the surrounding inflammatory cells. In vitro studies revealed that 
      TNF-alpha treatment showed a dose-dependent decrease of CDX2 messenger RNA (mRNA) and 
      protein expression in Caco-2 cells. Inhibition of nuclear factor-kappaB or p38 
      pathways showed that these are involved in the TNF-alpha-dependent downregulation of 
      CDX2. Furthermore, TNF-alpha-mediated downregulation of CDX2 was found to 
      significantly decrease the mRNA levels of adenomatous polyposis coli (APC), axis 
      inhibition protein 2 (AXIN2) and glycogen synthase kinase-3 beta (GSK3beta), whereas 
      the mRNA levels of Wnt targets were significantly elevated in TNF-alpha-treated 
      Caco-2 cells. These findings were associated with reduced binding of CDX2 to 
      promoter or enhancer regions of APC, AXIN2 and GSK3beta. In conclusion, it was found 
      that TNF-alpha induces the expression of Wnt signaling components through a 
      downregulation of the CDX2 expression that might have a tumor-promoting effect on 
      colon cancer cells.
FAU - Coskun, Mehmet
AU  - Coskun M
AD  - Department of Gastroenterology, Medical Section, Herlev Hospital, DK-2730 Herlev, 
      Denmark.
FAU - Olsen, Anders Kruger
AU  - Olsen AK
FAU - Bzorek, Michael
AU  - Bzorek M
FAU - Holck, Susanne
AU  - Holck S
FAU - Engel, Ulla Hojholt
AU  - Engel UH
FAU - Nielsen, Ole Haagen
AU  - Nielsen OH
FAU - Troelsen, Jesper Thorvald
AU  - Troelsen JT
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140205
PL  - England
TA  - Carcinogenesis
JT  - Carcinogenesis
JID - 8008055
RN  - 0 (CDX2 Transcription Factor)
RN  - 0 (CDX2 protein, human)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (beta Catenin)
SB  - IM
MH  - CDX2 Transcription Factor
MH  - Caco-2 Cells
MH  - Colonic Neoplasms/genetics/*metabolism
MH  - Gene Expression
MH  - Gene Expression Regulation, Neoplastic
MH  - Homeodomain Proteins/genetics/*metabolism
MH  - Humans
MH  - Immunohistochemistry
MH  - MAP Kinase Signaling System
MH  - NF-kappa B/metabolism
MH  - Protein Binding
MH  - Tumor Necrosis Factor-alpha/*metabolism
MH  - *Wnt Signaling Pathway
MH  - beta Catenin/genetics/metabolism
EDAT- 2014/02/07 06:00
MHDA- 2014/06/25 06:00
CRDT- 2014/02/07 06:00
PHST- 2014/02/07 06:00 [entrez]
PHST- 2014/02/07 06:00 [pubmed]
PHST- 2014/06/25 06:00 [medline]
AID - bgu037 [pii]
AID - 10.1093/carcin/bgu037 [doi]
PST - ppublish
SO  - Carcinogenesis. 2014 May;35(5):1185-92. doi: 10.1093/carcin/bgu037. Epub 2014 Feb 
      5.