Inhibition of Wnt-1 signaling induces apoptosis in beta-catenin-deficient mesothelioma cells.
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.
You
Liang
L
Thoracic Oncology Laboratory, Department of Surgery, Comprehensive Cancer Center, University of California, San Francisco, California 94115, USA.
He
Biao
B
Uematsu
Kazutsugu
K
Xu
Zhidong
Z
Mazieres
Julien
J
Lee
Amie
A
McCormick
Frank
F
Jablons
David M
DM
D017209:Apoptosis / Q000502:physiology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology; D008654:Mesothelioma / Q000235:genetics / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D014162:Transfection; D051153:Wnt Proteins; D051155:Wnt1 Protein; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D015534:Trans-Activators; C495247:WNT1 protein, human; D051153:Wnt Proteins; D051155:Wnt1 Protein; D051176:beta Catenin