The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
WNT-1 Signaling Inhibits Apoptosis by Activating β-Catenin/T Cell Factor–Mediated Transcription
Open accessAbstract
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 β-catenin/T cell factor (Tcf) transcription. Inhibition of β-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.
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Cites
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WNT signalling pathways as therapeutic targets in cancer
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GSK3 takes centre stage more than 20 years after its discovery
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Stem cell origin of cancer and differentiation therapy
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Metadata
- Authors
- Chen, S., Guttridge, D. C., You, Z., Zhang, Z., Fribley, A., Mayo, M. W., Kitajewski, J., & Wang, C.-Y.
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2001-01-08
- Volume
- 152
- Issue
- 1
- Pages
- 87-96
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- OpenAlex
- W1968366612
- Cited by
- 394
- References
- 8
- FWCI
- 7.27
- Type
- journal article
- Language
- en
- Open access
- green
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- Chen, S., Guttridge, D. C., You, Z., Zhang, Z., Fribley, A., Mayo, M. W., Kitajewski, J., & Wang, C.-Y. (2001). WNT-1 Signaling Inhibits Apoptosis by Activating β-Catenin/T Cell Factor–Mediated Transcription. The Journal of Cell Biology. https://doi.org/10.1083/jcb.152.1.87
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