Sunyana Gadal, Jacob A Boyer, Simon F Roy, Noah A Outmezguine, Malvika Sharma, Hongyan Li, Ning Fan, Eric Chan, Yevgeniy Romin, Afsar Barlas, Qing Chang, Priya Pancholi, Neilawattie Merna Timaul, Michael Overholtzer, Rona Yaeger, Katia Manova-Todorova, Elisa de Stanchina, Marcus Bosenberg, Neal Rosen
UNLABELLED: BRAF V600E mutation occurs in 46% of melanomas and drives high levels of ERK activity and ERK-dependent proliferation. However, BRAF V600E is insufficient to drive melanoma in GEMM models, and 82% of human benign nevi harbor BRAF V600E mutations. We show here that BRAF V600E inhibits mesenchymal migration by causing feedback inhibition of RAC1 activity. ERK pathway inhibition induces RAC1 activation and restores migration and invasion. In cells with BRAF V600E , mutant RAC1, overexpression of PREX1, PREX2, or PTEN inactivation restore RAC1 activity and cell motility...
April 20, 2024: bioRxiv