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ABSTRACT: The genetics of development and cancer have converged in the identification of intra- and extra-cellular signaling pathways that are aberrantly regulated in cancer and are also central to embryonic patterning. The Wnt signaling pathway has provided an outstanding example of this. The genes for β-catenin, APC, and Axin in the Wnt signaling pathway are often mutated in human cancers. In all such cases, the common denominator is the accumulation of cytosolic and nuclear β-catenin and the activation of transcriptional factor Tcf/Lef. The resulting gene expression profile should provide a significant clue as to cancers carrying defects in the Wnt signaling pathway. In this review, the regulation of the β-catenin stability by Axin and APC, and their genetic alterations in human cancers are described.