DiPRO1 distinctly reprograms muscle and mesenchymal cancer cells - Inrap - Institut national de recherches archéologiques préventives
Article Dans Une Revue EMBO Molecular Medicine Année : 2024

DiPRO1 distinctly reprograms muscle and mesenchymal cancer cells

Fayez Issa
Morgane Le-Gall
Pascal Maire

Résumé

Abstract We have recently identified the uncharacterized ZNF555 protein as a component of a productive complex involved in the morbid function of the 4qA locus in facioscapulohumeral dystrophy. Subsequently named DiPRO1 (Death, Differentiation, and PROliferation related PROtein 1), our study provides substantial evidence of its role in the differentiation and proliferation of human myoblasts. DiPRO1 operates through the regulatory binding regions of SIX1, a master regulator of myogenesis. Its relevance extends to mesenchymal tumors, such as rhabdomyosarcoma (RMS) and Ewing sarcoma, where DiPRO1 acts as a repressor via the epigenetic regulators TIF1B and UHRF1, maintaining methylation of cis-regulatory elements and gene promoters. Loss of DiPRO1 mimics the host defense response to virus, awakening retrotransposable repeats and the ZNF/KZFP gene family. This enables the eradication of cancer cells, reprogramming the cellular decision balance towards inflammation and/or apoptosis by controlling TNF-α via NF-kappaB signaling. Finally, our results highlight the vulnerability of mesenchymal cancer tumors to si/shDiPRO1-based nanomedicines, positioning DiPRO1 as a potential therapeutic target.

Dates et versions

hal-04697294 , version 1 (13-09-2024)

Licence

Domaine public

Identifiants

Citer

Jeremy Rich, Melanie Bennaroch, Laura Notel, Polina Patalakh, Julien Alberola, et al.. DiPRO1 distinctly reprograms muscle and mesenchymal cancer cells. EMBO Molecular Medicine, 2024, 16 (8), pp.1840-1885. ⟨10.1038/s44321-024-00097-z⟩. ⟨hal-04697294⟩
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