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Axin inhibits Lef-1 transcriptional activity in colon cancer cells : Chie SAKANAKA¹, Joseph B.WEISS² and Lewis T.WILLIAMS^1,3 (¹Cardiovascular Res.Inst.,Univ.of Calif.,San Francisco, ²Dept.of Dev.Biol.,Stanford Univ., School of Med.,³Chiron Corp.)

Axin is a molecule recently identified as a negative regulator of the Wnt pathway. In mammalian cells, we showed Axin inhibits Wnt-1 stimulation of β-catenin/Lymphoid enhancer factor 1 (Lef-1) dependent transcription. Axin also blocks β-catenin-mediated transcription in SW480 colon cancer cells that have a mutation in the adenomatous polyposis coli (APC) gene. We showed that Axin interacts GSK-3β and β-catenin directly and acts as a bridge between these molecules. From mutational analysis of Axin, the binding to both GSK-3β and β-catenin is necessary to an inhibitory effect of Axin on Lef-1 dependent transcriptional activity in colon cancer cells. In addition, we propose that the C-terminus region of Axin, which shares loose homology with Dsh, is crucial for its inhibitory effect.