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?-Catenin is overexpressed in acute myeloid leukemia and promotes the stabilization and nuclear localization of ß-catenin
journal contribution
posted on 2023-06-09, 13:12 authored by Rhys MorganRhys Morgan, L Pearn, K Liddiard, S L Pumford, A K Burnett, A Tonks, R L DarleyCanonical Wnt signaling regulates the transcription of T-cell factor (TCF)-responsive genes through the stabilization and nuclear translocation of the transcriptional co-activator, ß-catenin. Overexpression of ß-catenin features prominently in acute myeloid leukemia (AML) and has previously been associated with poor clinical outcome. Overexpression of ?-catenin mRNA (a close homologue of ß-catenin) has also been reported in AML and has been linked to the pathogenesis of this disease, however, the relative roles of these catenins in leukemia remains unclear. Here we report that overexpression and aberrant nuclear localization of ?-catenin is frequent in AML. Significantly, ?-catenin expression was associated with ß-catenin stabilization and nuclear localization. Consistent with this, we found that ectopic ?-catenin expression promoted the stabilization and nuclear translocation of ß-catenin in leukemia cells. ß-Catenin knockdown demonstrated that both ?- and ß-catenin contribute to TCF-dependent transcription in leukemia cells. These data indicate that ?-catenin expression is a significant factor in the stabilization of ß-catenin in AML. We also show that although normal cells exclude nuclear translocation of both ?- and ß-catenin, this level of regulation is lost in the majority of AML patients and cell lines, which allow nuclear accumulation of these catenins and inappropriate TCF-dependent transcription.
History
Publication status
- Published
File Version
- Published version
Journal
LeukemiaISSN
1476-5551Publisher
Nature Publishing GroupExternal DOI
Issue
2Volume
27Page range
336-43Department affiliated with
- Biochemistry Publications
Research groups affiliated with
- Haematology Research Group Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2018-05-10First Open Access (FOA) Date
2018-05-10First Compliant Deposit (FCD) Date
2018-05-09Usage metrics
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