FoxO3 suppresses Myc-driven lymphomagenesis

Cell Death & Disease
C J VandenbergS Cory

Abstract

This study demonstrates, for the first time, that loss of a single forkhead box class O (FoxO) transcription factor, can promote lymphomagenesis. Using two different mouse models, we show that FoxO3 has a significant tumour-suppressor function in the context of Myc-driven lymphomagenesis. Loss of FoxO3 significantly accelerated myeloid tumorigenesis in vavP-MYC10 transgenic mice and B lymphomagenesis in Eμ-myc transgenic mice. Tumour analysis indicated that the selective pressure for mutation of the p53 pathway during Eμ-myc lymphomagenesis was not altered. Frank tumours were preceded by elevated macrophage numbers in FoxO3(-/-) vavP-MYC10 mice but, surprisingly, pre-B-cell numbers were relatively normal in healthy young FoxO3(-/-)Eμ-myc mice. In vitro assays revealed enhanced survival capacity of Myc-driven cells lacking FoxO3, but no change in cell cycling was detected. The loss of FoxO3 may also be affecting other tumour-suppressive functions for which FoxO1/4 cannot fully compensate.

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Citations

Aug 12, 2017·Cell Death and Differentiation·Kirsteen J CampbellSuzanne Cory
May 22, 2018·Current Opinion in Hematology·Vijay Menon, Saghi Ghaffari
Dec 21, 2016·The Journal of Biological Chemistry·Carolina L BigarellaSaghi Ghaffari
Jun 19, 2020·International Journal of Molecular Sciences·Eleonora VecchioIleana Quinto
May 4, 2018·Oncoimmunology·Beata PyrzynskaMagdalena Winiarska
Apr 16, 2020·Trends in Genetics : TIG·Guillermo Martínez Corrales, Nazif Alic

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Methods Mentioned

BETA
acetylation
ubiquitination
nuclear translocation
flow cytometry
fluorescence-activated cell sorting

Software Mentioned

GraphPad
FlowJo
TreeStar
GraphPad Prism

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