Abstract
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 NH(2)-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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / physiology*
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Carcinoma, Non-Small-Cell Lung / genetics
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Carcinoma, Non-Small-Cell Lung / pathology
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Cytoskeletal Proteins / deficiency*
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Cytoskeletal Proteins / genetics
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Cytoskeletal Proteins / physiology
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Humans
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Lung Neoplasms / genetics
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Lung Neoplasms / pathology
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Mesothelioma / genetics
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Mesothelioma / pathology*
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Proto-Oncogene Proteins / antagonists & inhibitors*
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Proto-Oncogene Proteins / physiology
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RNA, Small Interfering / administration & dosage
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RNA, Small Interfering / genetics
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Signal Transduction / physiology
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Trans-Activators / deficiency*
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Trans-Activators / genetics
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Trans-Activators / physiology
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Transfection
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Wnt Proteins
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Wnt1 Protein
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beta Catenin
Substances
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CTNNB1 protein, human
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Cytoskeletal Proteins
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Proto-Oncogene Proteins
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RNA, Small Interfering
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Trans-Activators
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WNT1 protein, human
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Wnt Proteins
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Wnt1 Protein
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beta Catenin