Tyrosine kinase inhibitor STI-571/Gleevec down-regulates the beta-catenin signaling activity.
Tyrosine kinase inhibitor STI-571/Gleevec down-regulates the beta-catenin signaling activity.
复制标题
DOI：
10.1016/s0304-3835(03)00013-2
复制
发表时间：
2003-04
期刊：
影响因子：
9.7
通讯作者：
Lan Zhou;N. An;R. Haydon;Qixin Zhou;Hongwei Cheng;Ying Peng;Wei Jiang;H. Luu;P. Vanichakarn;J. Szatkowski;Jae Yoon Park;B. Breyer;T. He
中科院分区：
文献类型：
--
作者：
Lan Zhou;N. An;R. Haydon;Qixin Zhou;Hongwei Cheng;Ying Peng;Wei Jiang;H. Luu;P. Vanichakarn;J. Szatkowski;Jae Yoon Park;B. Breyer;T. He
β-Catenin是Wnt信号通路的关键转导子，在许多发育和细胞过程中发挥重要作用。在广泛的人类肿瘤中已经观察到β-连环蛋白信号转导的失调。在这篇报告中，我们研究了酪氨酸激酶抑制剂STI-571是否可以抑制β-catenin信号传导活性，从而抑制细胞增殖。我们的结果表明，STI-571有效地抑制了人结肠癌细胞中β-连环蛋白信号传导的组成性活性，以及HOS、HTB-94和HEK 293细胞中Wnt 1诱导的β-连环蛋白信号传导的激活。此外，STI-571显示出有效抑制人结肠癌细胞的增殖。最后，我们证明了STI-571有效地抑制了Wnt 1介导的GAL 4-β-catenin异源转录系统的激活。因此，我们的研究结果表明，酪氨酸磷酸化可能在调节β-catenin信号传导活性中发挥重要作用，STI-571对该信号传导途径的抑制可能进一步探索作为更广泛人类癌症替代/辅助治疗的重要靶点。
β-Catenin is a critical transducer of the Wnt signal pathway and plays an important role in many developmental and cellular processes. Deregulation of β-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 β-catenin signaling activity and hence suppress cell proliferation. Our results demonstrated that STI-571 effectively inhibited the constitutive activity of β-catenin signaling in human colon cancer cells as well as the Wnt1-induced activation of β-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-β-catenin heterologous transcription system was effectively inhibited by STI-571. Thus, our findings suggest that tyrosine phosphorylation may play an important role in regulating β-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.