DiPRO1 distinctly reprograms muscle and mesenchymal cancer cells.

DiPRO1 Mesenchymal Cancer Methylation Muscle Retrotransposable Repeats

Journal

EMBO molecular medicine
ISSN: 1757-4684
Titre abrégé: EMBO Mol Med
Pays: Germany
ID NLM: 101487380

Informations de publication

Date de publication:
15 Jul 2024
Historique:
received: 10 01 2023
accepted: 18 06 2024
revised: 13 06 2024
medline: 16 7 2024
pubmed: 16 7 2024
entrez: 15 7 2024
Statut: aheadofprint

Résumé

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.

Identifiants

pubmed: 39009887
doi: 10.1038/s44321-024-00097-z
pii: 10.1038/s44321-024-00097-z
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Société Française de lutte contre les Cancers et les leucémies de l'Enfant et de l'Adolescent (SFCE)
ID : W381005059
Organisme : Institut National de la Santé et de la Recherche Médicale (Inserm)
ID : ENV201416
Organisme : Institut Gustave-Roussy (Gustave Roussy)
ID : X75390

Informations de copyright

© 2024. The Author(s).

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Auteurs

Jeremy Rich (J)

UMR8126 CNRS, Gustave Roussy Cancer campus, Université Paris-Saclay, Villejuif, France.

Melanie Bennaroch (M)

UMR8126 CNRS, Gustave Roussy Cancer campus, Université Paris-Saclay, Villejuif, France.

Laura Notel (L)

UMR8126 CNRS, Gustave Roussy Cancer campus, Université Paris-Saclay, Villejuif, France.

Polina Patalakh (P)

UMR8126 CNRS, Gustave Roussy Cancer campus, Université Paris-Saclay, Villejuif, France.

Julien Alberola (J)

UMR8126 CNRS, Gustave Roussy Cancer campus, Université Paris-Saclay, Villejuif, France.

Fayez Issa (F)

INSERM U1016, CNRS UMR 8104, Institut Cochin, Université Paris-Cité, Paris, France.

Paule Opolon (P)

Pathology and Cytology Section, UMS AMMICA, CNRS, INSERM, Gustave Roussy Cancer campus, Université Paris-Saclay, Villejuif, France.

Olivia Bawa (O)

Pathology and Cytology Section, UMS AMMICA, CNRS, INSERM, Gustave Roussy Cancer campus, Université Paris-Saclay, Villejuif, France.

Windy Rondof (W)

Bioinformatics Platform, UMS AMMICA, CNRS, INSERM, Gustave Roussy Cancer campus, Université Paris-Saclay, Villejuif, France.
Department of Pediatric and Adolescent Oncology, Gustave Roussy Cancer campus, INSERM U1015, Université Paris-Saclay, Villejuif, France.

Antonin Marchais (A)

Bioinformatics Platform, UMS AMMICA, CNRS, INSERM, Gustave Roussy Cancer campus, Université Paris-Saclay, Villejuif, France.
Department of Pediatric and Adolescent Oncology, Gustave Roussy Cancer campus, INSERM U1015, Université Paris-Saclay, Villejuif, France.

Philippe Dessen (P)

Bioinformatics Platform, UMS AMMICA, CNRS, INSERM, Gustave Roussy Cancer campus, Université Paris-Saclay, Villejuif, France.

Guillaume Meurice (G)

Bioinformatics Platform, UMS AMMICA, CNRS, INSERM, Gustave Roussy Cancer campus, Université Paris-Saclay, Villejuif, France.

Morgane Le-Gall (M)

Proteom'IC facility, Université Paris Cité, CNRS, INSERM, Institut Cochin, F-75014, Paris, France.

Melanie Polrot (M)

Pre-clinical Evaluation Unit (PFEP), INSERM, Gustave Roussy Cancer campus, Université Paris-Saclay, Villejuif, France.

Karine Ser-Le Roux (K)

Pre-clinical Evaluation Unit (PFEP), INSERM, Gustave Roussy Cancer campus, Université Paris-Saclay, Villejuif, France.

Kamel Mamchaoui (K)

Sorbonne Université, Inserm, Institut de Myologie, Centre de Recherche en Myologie, F-75013, Paris, France.

Nathalie Droin (N)

Genomic Platform, UMS AMMICA US 23 INSERM UAR 3655 CNRS, Gustave Roussy Cancer campus, Université Paris-Saclay, Villejuif, France.
UMR1287 INSERM, Gustave Roussy Cancer campus, Université Paris-Saclay, Villejuif, France.

Hana Raslova (H)

UMR1287 INSERM, Gustave Roussy Cancer campus, Université Paris-Saclay, Villejuif, France.

Pascal Maire (P)

INSERM U1016, CNRS UMR 8104, Institut Cochin, Université Paris-Cité, Paris, France.

Birgit Geoerger (B)

Department of Pediatric and Adolescent Oncology, Gustave Roussy Cancer campus, INSERM U1015, Université Paris-Saclay, Villejuif, France.

Iryna Pirozhkova (I)

UMR8126 CNRS, Gustave Roussy Cancer campus, Université Paris-Saclay, Villejuif, France. iryna.pirozhkova@cnrs.fr.
INSERM U1016, CNRS UMR 8104, Institut Cochin, Université Paris-Cité, Paris, France. iryna.pirozhkova@cnrs.fr.

Classifications MeSH