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Molecular and Cellular Biology, March 2006, p. 2055-2064, Vol. 26, No. 6
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.6.2055-2064.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Novel Cross Talk of Krüppel-Like Factor 4 and ß-Catenin Regulates Normal Intestinal Homeostasis and Tumor Repression

Wen Zhang,^1,6, Xi Chen,^1,6, Yoichi Kato,² Paul M. Evans,^1,6 Subo Yuan,³ Jun Yang,^1,6 Piotr G. Rychahou,³ Vincent W. Yang,⁴ Xi He,⁵ B. Mark Evers,^3,6 and Chunming Liu^1,6*

Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas 77555,¹ Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, Florida 32306,² Department of Surgery, University of Texas Medical Branch, Galveston, Texas 77555,³ Division of Digestive Diseases, Emory University School of Medicine, Atlanta, Georgia 30322,⁴ Division of Neuroscience, Children's Hospital-Harvard Medical School, Boston, Massachusetts 02115,⁵ Sealy Center for Cancer Cell Biology, University of Texas Medical Branch, Galveston, Texas 77555⁶

Received 29 September 2005/ Returned for modification 28 November 2005/ Accepted 22 December 2005

Epithelial cells of the intestinal mucosa undergo a continual process of proliferation, differentiation, and apoptosis which is regulated by multiple signaling pathways. The Wnt/ß-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 ß-catenin and represses ß-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 ß-catenin plays a critical role in homeostasis of the normal intestine as well as in tumorigenesis of colorectal cancers.

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* Corresponding author. Mailing address: Sealy Center for Cancer Cell Biology, University of Texas Medical Branch, Galveston, TX 77555-1048. Phone: (409) 747-1090. Fax: (409) 747-1938. E-mail: chliu{at}utmb.edu.

Supplemental material for this article may be found at http://mcb.asm.org/.

W.Z. and X.C. contributed equally to this work.

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Molecular and Cellular Biology, March 2006, p. 2055-2064, Vol. 26, No. 6
0022-538X/06/$08.00+0     doi:10.1128/MCB.26.6.2055-2064.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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