Targeted inhibition of protein synthesis renders cancer cells vulnerable to apoptosis by unfolded protein response.

ABSTRACT: Cellular stress responses including the unfolded protein response (UPR) decide over the fate of an individual cell to ensure survival of the entire organism. During physiologic UPR counter-regulation, protective proteins are upregulated to prevent cell death. A similar strategy induces resistance to UPR in cancer. Therefore, we hypothesized that blocking protein synthesis following induction of UPR substantially enhances drug-induced apoptosis of malignant cells. In line, upregulation of the chaperone BiP was prevented by simultaneous arrest of protein synthesis in B cell malignancies. Cytotoxicity by immunotoxins-approved inhibitors of protein synthesis-was synergistically enhanced in combination with UPR-inducers in seven distinct hematologic and three solid tumor entities in vitro. Syne

SUBMITTER: Gsottberger F 

PROVIDER: S-EPMC10457359 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature