Activation of the Ataxia Telangiectasia Mutated/Autophagy pathway by a G-quadruplex ligand links senescence with apoptosis

Jennifer Beauvarlet; Jean-Louis Mergny; Mojgan Djavaheri-Mergny

doi:10.1080/23723556.2019.1604047

Activation of the Ataxia Telangiectasia Mutated/Autophagy pathway by a G-quadruplex ligand links senescence with apoptosis

Mol Cell Oncol. 2019 May 8;6(4):1604047. doi: 10.1080/23723556.2019.1604047. eCollection 2019.

Authors

Jennifer Beauvarlet¹, Jean-Louis Mergny^{2

3

4

5}, Mojgan Djavaheri-Mergny^{1

6

7}

Affiliations

¹ INSERM U1218, Institut Bergonié, Université de Bordeaux, Bordeaux, France.
² Institut Curie, PSL Research University, CNRS-UMR 9187, INSERM U1196, Orsay, France.
³ Université Paris Sud, Université Paris-Saclay, CNRS-UMR 9187, INSERM U1196, Orsay, France.
⁴ Université de Bordeaux, INSERM U1212, CNRS UMR 5320, ARNA Laboratory, IECB, Pessac, France.
⁵ Institute of Biophysics of the Czech Academy of Sciences, Brno, Czech Republic.
⁶ Equipe labellisée par la Ligue contre le cancer, Université Paris Descartes, Université Sorbonne Paris Cité, Université Paris Diderot, Sorbonne Université, INSERM U1138, Centre de Recherche des Cordeliers, Paris, France.
⁷ Metabolomics and Cell Biology Platforms, Institut Gustave Roussy, Villejuif, France.

Abstract

G-quadruplex (G4) ligands have shown anti-tumor activity by stabilizing G4 structures. We recently reported that the G4 ligand 20A promotes senescence in cancer cells through Ataxia Telangiectasia Mutated (ATM) and autophagy activation. Inhibition of both pathways directs cells to apoptosis, positioning ATM/autophagy axis as a linchpin between senescence and apoptosis.

Keywords: Cancer therapy; DNA damage response; G-quadruplex; autophagy; senescence.

Grants and funding

This work was supported by funds from the Institut National de la Santé et de la Recherche Médicale (INSERM), the University of Bordeaux, Institut Curie, the Bergonié Institute, the Conseil Regional d’Aquitaine, the Ligue contre le Cancer, Comité de Dordogne and the SYMBIT project (reg. no. CZ.02.1.01/0.0/0.0/15_003/0000477) financed by the ERDF.