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?-Catenin is overexpressed in acute myeloid leukemia and promotes the stabilization and nuclear localization of ß-catenin

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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 Darley
Canonical 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

Leukemia

ISSN

1476-5551

Publisher

Nature Publishing Group

Issue

2

Volume

27

Page range

336-43

Department affiliated with

  • Biochemistry Publications

Research groups affiliated with

  • Haematology Research Group Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2018-05-10

First Open Access (FOA) Date

2018-05-10

First Compliant Deposit (FCD) Date

2018-05-09

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