The atonal proneural transcription factor links differentiation and tumor formation in Drosophila.

The acquisition of terminal cell fate and onset of differentiation are instructed by cell type-specific master control genes. Loss of differentiation is frequently observed during cancer progression, but the underlying causes and mechanisms remain poorly understood. We tested the hypothesis that mas...

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Bibliographic Details
Main Authors: Wouter Bossuyt, Natalie De Geest, Stein Aerts, Iris Leenaerts, Peter Marynen, Bassem A Hassan
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2009-02-01
Series:PLoS Biology
Online Access:http://europepmc.org/articles/PMC2652389?pdf=render
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Summary:The acquisition of terminal cell fate and onset of differentiation are instructed by cell type-specific master control genes. Loss of differentiation is frequently observed during cancer progression, but the underlying causes and mechanisms remain poorly understood. We tested the hypothesis that master regulators of differentiation may be key regulators of tumor formation. Using loss- and gain-of-function analyses in Drosophila, we describe a critical anti-oncogenic function for the atonal transcription factor in the fly retina, where atonal instructs tissue differentiation. In the tumor context, atonal acts by regulating cell proliferation and death via the JNK stress response pathway. Combined with evidence that atonal's mammalian homolog, ATOH1, is a tumor suppressor gene, our data support a critical, evolutionarily conserved, function for ato in oncogenesis.
ISSN:1544-9173
1545-7885