Deficiency of ERO1 and activation of protein translation synergistically impair breast tumor resilience

ABSTRACT: Endoplasmic reticulum (ER) stress triggers an adaptive response which fosters tumor cell survival and resilience to stress conditions. Activation of the endoplasmic reticulum stress response, through its PERK branch, promotes the phosphorylation of the α-subunit of translation initiation factor eIF2alpha, thereby repressing general protein translation and selectively augmenting the translation of ATF4 with the downstream CHOP transcription factor and the protein disulfide oxidase ERO1. Here, we show that ISRIB, a small molecule, which inhibits the action of the phosphorylated α-subunit of eIF2, thereby activating protein translation, synergistically interacts with the genetic deficiency of protein disulfide oxidase ERO1 enfeebling tumor growth and spreading. ISRIB represses CHOP signal but

INSTRUMENT(S): NextSeq 500

ORGANISM(S): Homo sapiens

SUBMITTER: Marco Bolis 

PROVIDER: E-MTAB-11313 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress