TOE1 is a β-catenin interacting protein regulating the proliferation of hematopoietic cells through PAK2 modulation

Acute myeloid leukemia (AML) is an aggressive hematological malignancy frequently exhibiting deregulated expression/activity/localization of the Wnt signaling mediator β-catenin. To derive more effective β-catenin targeting strategies, we previously interrogated its interaction network in myeloid cells and identified several putative novel interacting partners, including Target of EGR1 (TOE1); a deadenylase with unknown function in hematological tissue. This study aimed to define TOE1 function in hematopoietic cells and uncover its molecular targets. TOE1 interacted with β-catenin in both primary and immortalized AML cells, and impacted Wnt signaling output through the modulation of lymphoid enhancer-binding factor-1 (LEF-1). AML samples exhibited deregulated TOE1 expression versus normal hematopoietic stem/progenitor cells (HSPCs), and TOE1 depletion suppressed the proliferation of myeloid leukemia cell lines, and primary human HSPCs, partly through a p21-activated-kinase 2 (PAK2) mediated mechanism. In summary, these data reveal TOE1 as a novel regulator of hematopoietic cell proliferation via the modulation of important growth-regulating pathways.