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Activation of caspase-2 by FASN inhibitors is mediated by the mTOR pathway. Upon FASN inhibition, the mTOR inhibitory protein REDD1 is induced and stimulates caspase-2 activation and apoptosis in FASN-sensitive ovarian cancer cells. On the other hand, in FASN-resistant ovarian cancer cells, REDD1 induction is impaired, but mTOR inhibitor treatment can substitute function of REDD1 and restore caspase-2-mediated sensitization of cells to apoptosis.
