Targeting PKC as a Therapeutic Strategy to Overcome Chemoresistance in TNBC by Restoring Aurora Kinase B Expression.

ABSTRACT: Triple-negative breast cancer (TNBC) poses a significant challenge due to its high mortality rates, primarily attributed to resistance against chemotherapy regimens containing taxanes like paclitaxel. Thus, developing combinatorial strategies to override resistance is a pressing need. By taking advantage of a library screening with various kinase inhibitors, we found that the small-molecule inhibitor enzastaurin targeting protein kinase C (PKC) could overcome resistance in TNBC cells. Mechanistically, dual treatment with paclitaxel and enzastaurin resulted in efficient mitotic arrest and subsequent cell death by restoring AURKB expression. Further analysis revealed that the GCN2-p-eIF2α axis was responsible for the posttranscriptional accumulation of AURKB upon combinatorial treatment. Fin

SUBMITTER: Cheng B 

PROVIDER: S-EPMC11915661 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature