The Wnt/beta-catenin signaling pathway targets PPARgamma activity in colon cancer cells.
Control of colon cell fate in adenocarcinomas is disrupted, in part, due to aberrant Wnt/beta-catenin signaling. The nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARgamma) has been implicated in the development of colon cancers. In the adenomatous polyposis coli multiple intestinal neoplasia (APCMin) mouse cancer model, PPARgamma expression in the colonic mucosa is markedly altered. In addition, PPARgamma protein levels are elevated, possibly through sequestration by activated beta-catenin in colon cancer cell lines. Induction of the Wnt/beta-catenin pathway by LiCl also elevated PPARgamma levels and induced PPARgamma-dependent reporter and endogenous target genes. Mechanistically, PPARgamma, through interactions with beta-catenin and T cell transcription factor (Tcf)-4, may be a determinant of cell fate and is likely a target of the Wnt pathway in cancer cells.
Jansson
Emmelie A
EA
Microbiology and Tumor Biology Center, Karolinska Institutet, S-17177 Stockholm, Sweden.
Are
Alexandra
A
Greicius
Gediminas
G
Kuo
I-Chun
IC
Kelly
Denise
D
Arulampalam
Velmurugesan
V
Pettersson
Sven
S
D011125:Adenomatous Polyposis Coli / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D015820:Cadherins / Q000502:physiology*; D002460:Cell Line; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000502:physiology; D003110:Colonic Neoplasms; D003598:Cytoskeletal Proteins / Q000502:physiology*; D017931:DNA Primers; D017491:Genes, APC; D017930:Genes, Reporter; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D007413:Intestinal Mucosa / Q000502:physiology; D007668:Kidney; D051379:Mice; D047495:PPAR gamma / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000502:physiology*; D014162:Transfection; D051153:Wnt Proteins; D051176:beta Catenin
C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D015820:Cadherins; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D036341:Intercellular Signaling Peptides and Proteins; D047495:PPAR gamma; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D051176:beta Catenin