Oncotarget

Research Papers:

ALT cancer cells are specifically sensitive to lysine acetyl transferase inhibition

Dalal Bakhos-Douaihy, Chantal Desmaze, Maya Jeitany, Laurent R. Gauthier, Denis Biard, Marie-Pierre Junier, Hervé Chneiweiss and François D. Boussin _

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Oncotarget. 2019; 10:773-784. https://doi.org/10.18632/oncotarget.26616

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Abstract

Dalal Bakhos-Douaihy1,2,3,4, Chantal Desmaze1,2,3,4, Maya Jeitany1,2,3,4, Laurent R. Gauthier1,2,3,4, Denis Biard5, Marie-Pierre Junier6, Hervé Chneiweiss6 and François D. Boussin1,2,3,4

1Laboratoire de Radiopathologie, CEA, Institut de Radiobiologie Cellulaire et Moléculaire, Fontenay-aux-Roses, France

2INSERM U1276, Fontenay-aux-Roses, France

3Université Paris-Diderot, U1276, Fontenay-aux-Roses, France

4Université Paris-Sud, U1276, Fontenay-aux-Roses, France

5CEA, Institut de Biologie François Jacob, SEPIA, Team Cellular Engineering and Human Syndromes, Université Paris-Saclay, F-92265 Fontenay-aux-Roses, France

6Neuroscience Paris Seine-IBPS, CNRS UMR8246, Inserm U1130, Sorbonne Université, Paris, France

Correspondence to:

François D. Boussin, email: boussin@cea.fr

Keywords: alternative mechanism of telomere maintenance; PCAF; GCN5; ionizing radiation

Received: February 28, 2018     Accepted: December 20, 2018     Published: January 22, 2019

ABSTRACT

Some cancer cells elongate their telomeres through the ALT (alternative lengthening of telomeres) pathway, which is based on homologous recombination for the addition of telomere repeats without telomerase activity. General control non-derepressible 5 (GCN5) and P300/CBP-associated factor (PCAF), two homologous lysine acetyltransferases, exert opposite effects on the ALT pathway, inhibiting or favoring it respectively. Here we show that ALT cells are particularly sensitive to the inhibition of acetyltransferases activities using Anacardic Acid (AA). AA treatment recapitulates the effect of PCAF knockdown on several ALT features, suggesting that AA decreased the ALT mechanism through the inhibition of lysine transferase activity of PCAF, but not that of GCN5. Furthermore, AA specifically sensitizes human ALT cells to radiation as compared to telomerase-positive cells suggesting that the inhibition of lysine acetyltransferases activity may be used to increase the radiotherapy efficiency against ALT cancers.


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