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Metabolic adaptation underlies epigenetic reprogramming in chemotherapy resistant breast cancer
19/06/2019 @ 11 h 30 min - 12 h 30 min
Mathieu Lupien (Department of Medical Biophysics, University of Toronto)
Mercredi 19 juin à 11h30, amphithéâtre Antoine Lacassagne, Centre de Recherche de Paris
Cancer cell survival upon cytotoxic drug exposure leads to changes in cell identity which is directly regulated by the epigenome. Several metabolites serve as substrates or co-factors to chromatin-modifying enzymes, suggesting that metabolic adaptations can underlie change in cell fate. Here, we show that progression of triple-negative breast cancer (TNBC) to taxane-resistance is characterized by altered metabolism conductive to a distinct epigenetic identity of chemotherapy resistant versus sensitive TNBC. The unique epigenetic identity of chemotherapy resistant TNBC ensure repression of transposable elements DNA sequences, thereby preventing activation of the anti-oncogenic viral mimicry checkpoint. The therapeutic ramification of these observation will be described.