The cytotoxic action of BCI is not dependent on its stated DUSP1 or DUSP6 targets in neuroblastoma cells.

ABSTRACT: Neuroblastoma (NB) is a heterogeneous cancer of the sympathetic nervous system, which accounts for 7-10% of paediatric malignancies worldwide. Due to the lack of targetable molecular aberrations in NB, most treatment options remain relatively nonspecific. Here, we investigated the therapeutic potential of BCI, an inhibitor of DUSP1 and DUSP6, in cultured NB cells. BCI was cytotoxic in a range of NB cell lines and induced a short-lived activation of the AKT and stress-inducible MAP kinases, although ERK phosphorylation was unaffected. Furthermore, a phosphoproteomic screen identified significant upregulation of JNK signalling components and suppression in mTOR and R6K signalling. To assess the specificity of BCI, CRISPR-Cas9 was employed to introduce insertions and deletions in the DUSP1 an

SUBMITTER: Thompson EM 

PROVIDER: S-EPMC9249316 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature