Pharmacological or TRIB3-Mediated Suppression of ATF4 Transcriptional Activity Promotes Hepatoma Cell Resistance to Proteasome Inhibitor Bortezomib.

ABSTRACT: The proteasome is an appealing target for anticancer therapy and the proteasome inhibitor bortezomib has been approved for the treatment of several types of malignancies. However, the molecular mechanisms underlying cancer cell resistance to bortezomib remain poorly understood. In the current article, we investigate how modulation of the eIF2α-ATF4 stress pathway affects hepatoma cell response to bortezomib. Transcriptome profiling revealed that many ATF4 transcriptional target genes are among the most upregulated genes in bortezomib-treated HepG2 human hepatoma cells. While pharmacological enhancement of the eIF2α-ATF4 pathway activity results in the elevation of the activities of all branches of the unfolded protein response (UPR) and sensitizes cells to bortezomib toxicity, the suppress

SUBMITTER: Ord T 

PROVIDER: S-EPMC8150958 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature