Glioma-derived cancer stem cells are hypersensitive to proteasomal inhibition.

ABSTRACT: Although proteasome inhibitors (PIs) are used as anticancer drugs to treat various cancers, their relative therapeutic efficacy on stem cells vs. bulk cancers remains unknown. Here, we show that stem cells derived from gliomas, GSCs, are up to 1,000-fold more sensitive to PIs (IC₅₀, 27-70 nM) compared with their differentiated controls (IC₅₀, 47 to »100 μM). The stemness of GSCs correlates to increased ubiquitination, whose misregulation readily triggers apoptosis. PI-induced apoptosis of GSCs is independent of NF-κB but involves the phosphorylation of c-Jun N-terminal kinase as well as the transcriptional activation of endoplasmic reticulum (ER) stress-associated proapoptotic mediators. In contrast to the general notion that ER stress-associated apoptosis is signaled

SUBMITTER: Yoo YD 

PROVIDER: S-EPMC5210095 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature