Time-resolved Phosphoproteome Analysis of Paradoxical RAF Activation Reveals Novel Targets of ERK.

ABSTRACT: Small molecules targeting aberrant RAF activity, like vemurafenib (PLX4032), are highly effective against cancers harboring the V600E BRAF mutation and are now approved for clinical use against metastatic melanoma. However, in tissues showing elevated RAS activity and in RAS mutant tumors, these inhibitors stimulate RAF dimerization, resulting in inhibitor resistance and downstream "paradoxical" ERK activation. To understand the global signaling response of cancer cells to RAF inhibitors, we profiled the temporal changes of the phosphoproteome of two colon cancer cell lines (Colo205 and HCT116) that respond differently to vemurafenib. Comprehensive data mining and filtering identified a total of 37,910 phosphorylation sites, 660 of which were dynamically modulated upon treatment with vemur

SUBMITTER: Kubiniok P 

PROVIDER: S-EPMC5383785 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature