Novel cross talk of Kruppel-like factor 4 and beta-catenin regulates normal intestinal homeostasis and tumor repression.
Epithelial cells of the intestinal mucosa undergo a continual process of proliferation, differentiation, and apoptosis which is regulated by multiple signaling pathways. The Wnt/beta-catenin pathway plays a critical role in this process. Mutations in the Wnt pathway, however, are associated with colorectal cancers. Krüppel-like factor 4 (KLF4) is an epithelial transcriptional factor that is down-regulated in many colorectal cancers. Here, we show that KLF4 interacts with beta-catenin and represses beta-catenin-mediated gene expression. Moreover, KLF4 inhibits the axis formation of Xenopus embryos and inhibits xenograft tumor growth in athymic nude mice. Our findings suggest that the cross talk of KLF4 and beta-catenin plays a critical role in homeostasis of the normal intestine as well as in tumorigenesis of colorectal cancers.
Zhang
Wen
W
Sealy Center for Cancer Cell Biology, University of Texas Medical Branch, Galveston, TX 77555-1048, USA.
Chen
Xi
X
Kato
Yoichi
Y
Evans
Paul M
PM
Yuan
Subo
S
Yang
Jun
J
Rychahou
Piotr G
PG
Yang
Vincent W
VW
He
Xi
X
Evers
B Mark
BM
Liu
Chunming
C
D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015197:Carcinogenicity Tests; D002467:Cell Nucleus / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000209:etiology* / Q000235:genetics; D004625:Embryo, Nonmammalian; D005260:Female; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D017434:Protein Structure, Tertiary; D012016:Reference Values; D015398:Signal Transduction; D015533:Transcriptional Activation; D014981:Xenopus / Q000196:embryology; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D025601:Adenomatous Polyposis Coli Protein; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D051176:beta Catenin