PMID- 18177486
OWN - NLM
STAT- MEDLINE
DCOM- 20080512
LR  - 20101118
IS  - 1349-7006 (Electronic)
IS  - 1347-9032 (Linking)
VI  - 99
IP  - 4
DP  - 2008 Apr
TI  - Wnt signaling inside the nucleus.
PG  - 631-7
LID - 10.1111/j.1349-7006.2007.00716.x [doi]
AB  - Accumulation of the beta-catenin protein and transactivation of a certain set of 
      T-cell factor (TCF)-4 target genes by accumulated beta-catenin have been 
      considered crucial in colorectal carcinogenesis. In the present review, we 
      summarize nuclear proteins that interact with, and regulate, the beta-catenin and 
      TCF and lymphoid enhancer factor (LEF) transcriptional complexes. Our recent 
      series of proteomic studies has also revealed that various classes of nuclear 
      proteins participate in the beta-catenin-TCF-4 complex and modulate its 
      transcriptional activity. Furthermore, the protein composition of the 
      TCF-4-containing nuclear complex is not fixed, but is regulated dynamically by 
      endogenous programs associated with intestinal epithelial cell differentiation 
      and exogenous stimuli. Restoration of the loss-of-function mutation of the 
      adenomatous polyposis coli (APC) gene in colorectal cancer cells does not seem to 
      be a realistic approach with currently available medical technologies, and only 
      signaling molecules downstream of the APC gene product can be considered as 
      targets of pharmacological intervention. Nuclear proteins associated with the 
      beta-catenin-TCF-4 complex may include feasible targets for molecular therapy 
      against colorectal cancer. Recently, an inhibitor of the interaction between 
      CREB-binding protein and beta-catenin was shown to efficiently shut down the 
      transcriptional activity of TCF-4 and induce apoptosis of colorectal cancer 
      cells. We also summarize current strategies in the development of drugs against 
      Wnt signaling.
FAU - Shitashige, Miki
AU  - Shitashige M
AD  - Chemotherapy Division and Cancer Proteomics Project, National Cancer Center 
      Research Institute, 5-1-1 Tsukiji, Chuoh-ku, Tokyo 104-0045, Japan.
FAU - Hirohashi, Setsuo
AU  - Hirohashi S
FAU - Yamada, Tesshi
AU  - Yamada T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20080102
PL  - England
TA  - Cancer Sci
JT  - Cancer science
JID - 101168776
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Nuclear Proteins)
RN  - 0 (TCF Transcription Factors)
RN  - 0 (TCF7L2 protein, human)
RN  - 0 (Tcf7l2 protein, mouse)
RN  - 0 (Transcription Factor 7-Like 2 Protein)
RN  - 0 (Wnt Proteins)
RN  - 0 (beta Catenin)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*isolation & purification/pharmacology/therapeutic use
MH  - Cell Nucleus/metabolism
MH  - Colorectal Neoplasms/drug therapy/genetics/*metabolism
MH  - Drug Design
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Genes, APC
MH  - Humans
MH  - Male
MH  - Mice
MH  - Nuclear Proteins/drug effects/*metabolism
MH  - TCF Transcription Factors/antagonists & inhibitors/*metabolism
MH  - Transcription Factor 7-Like 2 Protein
MH  - Wnt Proteins/antagonists & inhibitors/*metabolism
MH  - beta Catenin/antagonists & inhibitors/*metabolism
RF  - 78
EDAT- 2008/01/08 09:00
MHDA- 2008/05/13 09:00
CRDT- 2008/01/08 09:00
PHST- 2008/01/08 09:00 [pubmed]
PHST- 2008/05/13 09:00 [medline]
PHST- 2008/01/08 09:00 [entrez]
AID - CAS716 [pii]
AID - 10.1111/j.1349-7006.2007.00716.x [doi]
PST - ppublish
SO  - Cancer Sci. 2008 Apr;99(4):631-7. doi: 10.1111/j.1349-7006.2007.00716.x. Epub 
      2008 Jan 2.