Identification of BMP and Activin Membrane-bound Inhibitor (BAMBI), an Inhibitor of Transforming Growth Factor-β Signaling, as a Target of the β-Catenin Pathway in Colorectal Tumor Cells

Takashi Sekiya, Shungo Adachi, Kazuyoshi Kohu, Tatsuya Yamada, Osamu Higuchi, Yoichi Furukawa, Yusuke Nakamura, Tsutomu Nakamura, Kousuke Tashiro, Satoru Kuhara, Susumu Ohwada, Tetsu Akiyama

Research output: Contribution to journalArticlepeer-review

121 Citations (Scopus)

Abstract

The Wnt signaling pathway is activated in most human colorectal tumors. Mutational inactivation in the tumor suppressor adenomatous polyposis coli (APC), as well as activation of β-catenin, causes the accumulation of β-catenin, which in turn associates with the T cell factor/lymphoid enhancer factor (TCF/LEF) family of transcription factors and activates transcription of their target genes. Here we show that β-catenin activates transcription of the BMP and activin membrane. bound inhibitor (BAMBI)/NMA gene. The expression level of BAMBI was found to be aberrantly elevated in most colorectal and hepatocellular carcinomas relative to the corresponding non-cancerous tissues. Expression of BAMBI in colorectal tumor cell lines was repressed by a dominant-negative mutant of TCF-4 of by an inhibitor of β-catenin-TCF interaction, suggesting that β-catenin is responsible for the aberrant expression of BAMBI in colorectal tumor cells. Furthermore, overexpression of BAMBI inhibited the response of tumor cells to transforming growth factor-β signaling. These results suggest that β-catenin interferes with transforming growth factor-β-mediated growth arrest by inducing the expression of BAMBI, and this may contribute to colorectal and hepatocellular tumorigenesis.

Original languageEnglish
Pages (from-to)6840-6846
Number of pages7
JournalJournal of Biological Chemistry
Volume279
Issue number8
DOIs
Publication statusPublished - Feb 20 2004

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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