Data from A CDK4/6-Dependent Epigenetic Mechanism Protects Cancer Cells from PML-induced Senescence

• DOI: 10.1158/0008-5472.c.6507690.v1
• Publication Date: 2023-04-01T01:27:17Z
• Authors: Mariana Acevedo; Mathieu Vernier; Lian Mignacca; Frédéric Lessard; Geneviève Huot; Olga Moiseeva; Véronique Bourdeau; Gerardo Ferbeyre
• Keywords: Senescence; Retinoblastoma protein

<div>Abstract<p>Promyelocytic leukemia (PML) plays a tumor suppressive role by inducing cellular senescence in response to oncogenic stress. However, cell lines fail engage complete upon PML activation. In this study, we investigated the mechanisms underlying resistance PML-induced senescence. Here, report that activation of cyclin-dependent kinases CDK4 and CDK6 are essential sufficient impair induced expression. Disrupting CDK function RNA interference or pharmacological inhibition restored cells diminished their tumorigenic potential mouse xenograft models. Complete correlated with an increase autophagy, repression E2F target genes, gene expression signature blocked DNA methylation. Accordingly, treatment inhibitors methylation reversed Further, palbociclib promoted autophagy-dependent degradation methyltransferase DNMT1. Lastly, found interacted phosphorylated DNMT1 <i>in vitro</i>, suggesting activity is required for its stabilization. Taken together, our findings highlight potentially valuable feature CDK4/6 as epigenetic modulators facilitate programs cells. <i>Cancer Res; 76(11); 3252–64. ©2016 AACR</i>.</p></div>