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DKK1, a negative regulator of Wnt signaling, is a target of the β-catenin/TCF pathway

Oncogene volume 23, pages 8520–8526 (2004)Cite this article

Abstract

Wnt signaling plays an important role in embryonic development and tumorigenesis. These biological effects are exerted by activation of the β-catenin/TCF transcription complex and consequent regulation of a set of downstream genes. TCF-binding elements have been found in the promoter regions of many TCF target genes and characterized by a highly conserved consensus sequence. Utilizing this consensus sequence, we performed an in silico screening for new TCF target genes. Through computational screening and subsequent experimental analysis, we identified a novel TCF target gene, DKK1, which has been shown to be a potent inhibitor of Wnt signaling. Our finding suggests the existence of a novel feedback loop in Wnt signaling.

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Acknowledgements

We thank S Adachi, K Satoh, A Nishida and T Moriguchi for helpful discussion. This work was supported by Grants-in-Aid for Scientific Research on Priority Areas and the Organization for Pharmaceutical Safety and Research.

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Authors and Affiliations

  1. Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-0032, Japan

    Atsushi Niida, Takatoshi Hiroko, Mana Kasai & Tetsu Akiyama

  2. Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokane-dai, Minato-ku, Tokyo, 108-8639, Japan

    Yoichi Furukawa & Yusuke Nakamura

  3. Laboratory of Genome Database, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan

    Yutaka Suzuki & Sumio Sugano

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  1. Atsushi Niida
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  2. Takatoshi Hiroko
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Correspondence to Tetsu Akiyama.

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Niida, A., Hiroko, T., Kasai, M. et al. DKK1, a negative regulator of Wnt signaling, is a target of the β-catenin/TCF pathway. Oncogene 23, 8520–8526 (2004). https://doi.org/10.1038/sj.onc.1207892

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