Wnt-1 signaling inhibits apoptosis by activating beta-catenin/T cell factor-mediated transcription.
J Cell Biol
; 152(1): 87-96, 2001 Jan 08.
Article
in En
| MEDLINE
| ID: mdl-11149923
ABSTRACT
Wnt signaling plays a critical role in development and oncogenesis. Although significant progress has been made in understanding the downstream signaling cascade of Wnt signaling, little is known regarding Wnt signaling modification of the cell death machinery. Given that numerous oncogenes transform cells by providing cell survival function, we hypothesized that Wnt signaling may inhibit apoptosis. Here, we report that cells expressing Wnt-1 were resistant to cancer therapy-mediated apoptosis. Wnt-1 signaling inhibited the cytochrome c release and the subsequent caspase-9 activation induced by chemotherapeutic drugs, including both vincristine and vinblastine. Furthermore, we found that Wnt-1-mediated cell survival was dependent on the activation of beta-catenin/T cell factor (Tcf) transcription. Inhibition of beta-catenin/Tcf transcription by expression of the dominant-negative mutant of Tcf-4 blocked Wnt-1-mediated cell survival and rendered cells sensitive to apoptotic stimuli. These results provide the first demonstration that Wnt-1 inhibits cancer therapy-mediated apoptosis and suggests that Wnt-1 may exhibit its oncogenic potential through a mechanism of anti-apoptosis.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transcription Factors
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Signal Transduction
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Transcriptional Activation
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Trans-Activators
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Proto-Oncogene Proteins
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Apoptosis
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Cytoskeletal Proteins
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Zebrafish Proteins
Limits:
Animals
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Humans
Language:
En
Journal:
J Cell Biol
Year:
2001
Document type:
Article
Affiliation country:
United States
Publication country:
EEUU
/
ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
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UNITED STATES
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UNITED STATES OF AMERICA
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US
/
USA