Adaptive translational reprogramming of metabolism limits the response to targeted therapy in BRAF^V600 melanoma.

ABSTRACT: Despite the success of therapies targeting oncogenes in cancer, clinical outcomes are limited by residual disease that ultimately results in relapse. This residual disease is often characterized by non-genetic adaptive resistance, that in melanoma is characterised by altered metabolism. Here, we examine how targeted therapy reprograms metabolism in BRAF-mutant melanoma cells using a genome-wide RNA interference (RNAi) screen and global gene expression profiling. Using this systematic approach we demonstrate post-transcriptional regulation of metabolism following BRAF inhibition, involving selective mRNA transport and translation. As proof of concept we demonstrate the RNA processing kinase U2AF homology motif kinase 1 (UHMK1) associates with mRNAs encoding metabolism proteins and selective

SUBMITTER: Smith LK 

PROVIDER: S-EPMC8888590 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature