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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Tyrosine kinase inhibitor STI-571/Gleevec down-regulates the beta-catenin signaling activity.

Beta-Catenin is a critical transducer of the Wnt signal pathway and plays an important role in many developmental and cellular processes. Deregulation of beta-catenin signaling has been observed in a broad range of human tumors. In this report, we investigated whether tyrosine kinase inhibitor STI-571 could inhibit the beta-catenin signaling activity and hence suppress cell proliferation. Our results demonstrated that STI-571 effectively inhibited the constitutive activity of beta-catenin signaling in human colon cancer cells as well as the Wnt1- induced activation of beta-catenin signaling in HOS, HTB-94, and HEK 293 cells. Furthermore, STI-571 was shown to effectively suppress the proliferation of human colon cancer cells. Finally, we demonstrated that the Wnt1-mediated activation of a GAL4-beta-catenin heterologous transcription system was effectively inhibited by STI-571. Thus, our findings suggest that tyrosine phosphorylation may play an important role in regulating beta-catenin signaling activity, and inhibition of this signaling pathway by STI-571 may be further explored as an important target for alternative/adjuvant treatments for a broader range of human cancer.[1]


  1. Tyrosine kinase inhibitor STI-571/Gleevec down-regulates the beta-catenin signaling activity. Zhou, L., An, N., Haydon, R.C., Zhou, Q., Cheng, H., Peng, Y., Jiang, W., Luu, H.H., Vanichakarn, P., Szatkowski, J.P., Park, J.Y., Breyer, B., He, T.C. Cancer Lett. (2003) [Pubmed]
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