Journal
CANCER RESEARCH
Volume 64, Issue 10, Pages 3474-3478Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-04-0115
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Funding
- NCI NIH HHS [R01 CA093708-01A3, R01 CA093708] Funding Source: Medline
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It is known that Wnt-1 signaling inhibits apoptosis by activating beta-catenin/tcf-mediated transcription. Here, we show that blocking Wnt-1 signaling in beta-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 beta-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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