Proof-of-principle: oncogenic beta-catenin is a valid molecular target for the development of pharmacological inhibitors.


Activation of beta-catenin is a critical step in the pathogenesis of many common human cancers and is the initiating event in adenocarcinoma of the colon. Because activation of beta-catenin provides a gain-of-function, it is tempting to speculate that specific pharmacological inhibition of activated beta-catenin might reverse the tumorigenic properties of human cancer cells and therefore form the basis of an effective anticancer strategy. In an effort to provide proof-of-principle for such a strategy, we used a novel clonal growth assay based on human somatic cell gene targeting to determine whether activated beta-catenin remains a necessary oncogenic stimulus in advanced human cancer cells. Using this approach, we demonstrate that beta-catenin is a necessary oncogene in human SW48 and DLD1 colon cancer cells but not in HCT116 cells. These data indicate that activated beta-catenin can remain a critical oncogenic stimulus throughout the progression of human colon cancer and suggest that the small molecule inhibitors of activated beta-catenin currently under development will be effective anticancer therapeutics in a subset of malignant colon cancers.

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@article{Kim2002ProofofprincipleOB, title={Proof-of-principle: oncogenic beta-catenin is a valid molecular target for the development of pharmacological inhibitors.}, author={J. Julie Kim and Heather Crooks and Aaron Foxworth and Todd Waldman}, journal={Molecular cancer therapeutics}, year={2002}, volume={1 14}, pages={1355-9} }