Skip to content

LEF-1 drives aberrant β-catenin nuclear localization in myeloid leukemia cells

Research output: Contribution to journalArticle

Original languageEnglish
Number of pages50
JournalHaematologica
Early online date10 Jan 2019
DOIs
DateAccepted/In press - 3 Jan 2019
DateE-pub ahead of print (current) - 10 Jan 2019

Abstract

Canonical Wnt/β-catenin signaling is frequently dysregulated in myeloid leukemias and is implicated in leukemogenesis. Nuclear-localized β-catenin is indicative of active Wnt signaling and is frequently observed in acute myeloid leukemia patients; however, some patients exhibit little or no nuclear β-catenin even where cytosolic β-catenin is abundant. Control of the subcellular localization of β-catenin therefore represents an additional mechanism regulating Wnt signaling in hematopoietic cells. To investigate the factors mediating the nuclear-localization of β-catenin we carried out the first nuclear/cytoplasmic proteomic analysis of the β-catenin interactome in myeloid leukemia cells and identified putative novel β-catenin interactors. Comparison of interacting factors between Wnt-responsive cells (high nuclear β-catenin) versus Wnt-unresponsive cells (low nuclear β-catenin) suggested the transcriptional partner, LEF-1, could direct the nuclear-localization of β-catenin. The relative levels of nuclear LEF-1 and β-catenin were tightly correlated in both cell lines and in primary AML blasts. Furthermore, LEF-1 knockdown perturbed β-catenin nuclear-localization and transcriptional activation in Wnt-responsive cells. Conversely, LEF-1 overexpression was able to promote both nuclear-localization and β-catenin-dependent transcriptional responses in previously Wnt-unresponsive cells. This is the first β-catenin interactome study in hematopoietic cells and reveals LEF-1 as a mediator of nuclear β-catenin level human myeloid leukemia.

    Research areas

  • acute myeloid leukemia, B-Catenin, LEF-1, Signal transduction, WNT signaling

Download statistics

No data available

Documents

Documents

  • Full-text PDF (final published version)

    Rights statement: This is the final published version of the article (version of record). It first appeared online via Ferrata Storti Foundation at https://doi.org/10.3324/haematol.2018.202846 . Please refer to any applicable terms of use of the publisher.

    Final published version, 2 MB, PDF-document

DOI

View research connections

Related faculties, schools or groups