GSE113424 Modulation of the ATM/autophagy pathway tips the balance between senescence and apoptosis in response to 20A ligand

Contributors : Jennifer Beauvarlet ; Paul B Sadoun ; Elodie Darbo ; Gaelle Labrunie ; Beno ît Rousseau ; Elodie Richard ; Rabindra N Das ; Guillaume Robert ; Jean-William Dupuy ; Francois Orange ; Sabrina Croce ; Valerie Valesco ; Pierre Soubeyran ; Kevin Ryan ; Jean-Louis Mergny ; Mojgan Djavaheri-MergnySeries Type : Expression profiling by arrayOrganism : Homo sapiensG-quadruplex ligands (G4L) exert their anti-proliferative effect through telomere-dependent and -independent mechanisms, but the inter-relationship between autophagy, cell growth arrest and cell death induced by these ligands remains largely unexplored. 20A is a 2,4,6-triarylpyridine derivative that binds to G4-DNA with fair to excellent selectivity. Here, we demonstrate that this compound impairs cancer cell viability through induction of senescence and apoptotic cell death in a p53-independent manner. In vivo results corroborate those obtained in in vitro, showing that 20A elicits an important tumor growth inhibition in HeLa-xenografted tumor model. The transcriptomic and proteomic analyses reveal the functional enrichment in the growth arrest, DDR and lysosomal pathways upon 20A treatment. More particularly, we find that ATM and autophagy are activated upon 20A treatment. Genetic inhibition of ATM following 20A treatment inhibits both autophagy and senescence and directs cells to apoptosis. Moreover, loss of autophagy by deletion of two essential autophagy genes ATG5 and ATG7 leads to failure ...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by array Homo sapiens Source Type: research