Inhibition of O-GlcNAcase Sensitizes Apoptosis and Reverses Bortezomib Resistance in Mantle Cell Lymphoma through Modification of Truncated Bid.

ABSTRACT: Aberrant energy metabolism represents a hallmark of cancer and contributes to numerous aggressive behaviors of cancer cells, including cell death and survival. Despite the poor prognosis of mantle cell lymphoma (MCL), due to the inevitable development of drug resistance, metabolic reprograming of MCL cells remains an unexplored area. Posttranslational modification of proteins via O-GlcNAcylation is an ideal sensor for nutritional changes mediated by O-GlcNAc transferase (OGT) and is removed by O-GlcNAcase (OGA). Using various small-molecule inhibitors of OGT and OGA, we found for the first time that O-GlcNAcylation potentiates MCL response to bortezomib. CRISPR interference of MGEA5 (encoding OGA) validated the apoptosis sensitization by O-GlcNAcylation and OGA inhibition. To identify the

SUBMITTER: Luanpitpong S 

PROVIDER: S-EPMC5805589 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature