Genomic Deletion of Malic Enzyme 2 Confers Collateral Lethality in Pancreatic Cancer

Homozygous deletion of SMAD4 often results in loss of the neighboring metabolic gene malic enzyme 2 (ME2), creating a cancer-specific metabolic vulnerability upon targeting of its paralogous isoform ME3. Here we show that ME3 depletion selectively kills ME2-null PDAC cells in a manner consistent with an essential function for ME3 in these cancer cells. These data extended and further validated the concept of ‘collateral lethality’.

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