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Article Dans Une Revue Nature Année : 2024

Transient loss of Polycomb components induces an epigenetic cancer fate

Chetan C. Rawal
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M. Erokhin
Marco Di Stefano
N. Butova
I. Chiolo
D. Chetverina
A.-M. Martinez
Giacomo Cavalli
Davide Normanno

Résumé

Although cancer initiation and progression are generally associated with the accumulation of somatic mutations 1,2 , substantial epigenomic alterations underlie many aspects of tumorigenesis and cancer susceptibility 3–6 , suggesting that genetic mechanisms might not be the only drivers of malignant transformation 7 . However, whether purely non-genetic mechanisms are sufficient to initiate tumorigenesis irrespective of mutations has been unknown. Here, we show that a transient perturbation of transcriptional silencing mediated by Polycomb group proteins is sufficient to induce an irreversible switch to a cancer cell fate in Drosophila . This is linked to the irreversible derepression of genes that can drive tumorigenesis, including members of the JAK–STAT signalling pathway and zfh1 , the fly homologue of the ZEB1 oncogene, whose aberrant activation is required for Polycomb perturbation-induced tumorigenesis. These data show that a reversible depletion of Polycomb proteins can induce cancer in the absence of driver mutations, suggesting that tumours can emerge through epigenetic dysregulation leading to inheritance of altered cell fates.
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Dates et versions

hal-04581411 , version 1 (22-05-2024)

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Victoria Parreno, Vincent Loubiere, Bernd Schuettengruber, Lauriane Fritsch, Chetan C. Rawal, et al.. Transient loss of Polycomb components induces an epigenetic cancer fate. Nature, 2024, 629 (8012), pp.688-696. ⟨10.1038/s41586-024-07328-w⟩. ⟨hal-04581411⟩
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