CDYL2 Epigenetically Regulates MIR124 to Control NF-κB/STAT3-Dependent Breast Cancer Cell Plasticity.
Fiche publication
Date publication
mai 2020
Journal
iScience
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GRONEMEYER Hinrich
Tous les auteurs :
Siouda M, Dujardin AD, Barbollat-Boutrand L, Mendoza-Parra MA, Gibert B, Ouzounova M, Bouaoud J, Tonon L, Robert M, Foy JP, Lavergne V, Manie SN, Viari A, Puisieux A, Ichim G, Gronemeyer H, Saintigny P, Mulligan P
Lien Pubmed
Résumé
Epigenetic deregulation of gene transcription is central to cancer cell plasticity and malignant progression but remains poorly understood. We found that the uncharacterized epigenetic factor chromodomain on Y-like 2 (CDYL2) is commonly over-expressed in breast cancer, and that high CDYL2 levels correlate with poor prognosis. Supporting a functional role for CDYL2 in malignancy, it positively regulated breast cancer cell migration, invasion, stem-like phenotypes, and epithelial-to-mesenchymal transition. CDYL2 regulation of these plasticity-associated processes depended on signaling via p65/NF-κB and STAT3. This, in turn, was downstream of CDYL2 regulation of MIR124 gene transcription. CDYL2 co-immunoprecipitated with G9a/EHMT2 and GLP/EHMT1 and regulated the chromatin enrichment of G9a and EZH2 at MIR124 genes. We propose that CDYL2 contributes to poor prognosis in breast cancer by recruiting G9a and EZH2 to epigenetically repress MIR124 genes, thereby promoting NF-κB and STAT3 signaling, as well as downstream cancer cell plasticity and malignant progression.
Mots clés
Cancer, Functional Aspects of Cell Biology, Molecular Mechanism of Gene Regulation, Stem Cells Research
Référence
iScience. 2020 May 6;23(6):101141