BRAF inhibition sensitizes melanoma cells to α-amanitin via decreased RNA polymerase II assembly.

ABSTRACT: Despite the great success of small molecule inhibitors in the treatment of patients with BRAF^V600E mutated melanoma, the response to these drugs remains transient and patients eventually relapse within a few months, highlighting the need to develop novel combination therapies based on the understanding of the molecular changes induced by BRAF^V600E inhibitors. The acute inhibition of oncogenic signaling can rewire entire cellular signaling pathways and thereby create novel cancer cell vulnerabilities. Here, we demonstrate that inhibition of BRAF^V600E oncogenic signaling in melanoma cell lines leads to destabilization of the large subunit of RNA polymerase II POLR2A (polymerase RNA II DNA-directed polypeptide A), thereby preventing its binding to the unconven

SUBMITTER: Frischknecht L 

PROVIDER: S-EPMC6533289 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature