Inhibition of Wnt-1 Signaling Induces Apoptosis in β-Catenin-Deficient Mesothelioma Cells

Cancer Research - Tập 64 Số 10 - Trang 3474-3478 - 2004
Liang You1, Biao He1, Kazutsugu Uematsu1, Zhidong Xu1, Julien Mazières1, Amie Y. Lee1, Frank McCormick1, David M. Jablons1
1Thoracic Oncology Laboratory, Department of Surgery, Comprehensive Cancer Center, University of California, San Francisco, California

Tóm tắt

Abstract It is known that Wnt-1 signaling inhibits apoptosis by activating β-catenin/tcf-mediated transcription. Here, we show that blocking Wnt-1 signaling in β-catenin-deficient mesothelioma cell lines H28 and MS-1 induces apoptotic cell death. Both Wnt-1 small interfering RNA (siRNA) and Dishevelled siRNA induced significant apoptosis in these cell lines. A small molecule inhibitor of c-Jun NH2-terminal kinase inhibited the apoptotic cell killing induced by either Wnt-1 siRNA or Dishevelled siRNA in these cells. Our data suggest that β-catenin-independent noncanonical pathway(s), i.e., Wnt/JNK pathway, may play a role in the apoptotic inhibition caused by Wnt-1 signaling.

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