Article
Tumorigenesis Driven by BRAFV600E Requires Secondary Mutations That Overcome Its Feedback Inhibition of RAC1 and Migration.
Cancer research - 2 May 2025
Gadal Sunyana, Boyer Jacob A, Roy Simon F, Outmezguine Noah A, Sharma Malvika, Li Hongyan, Fan Ning, Chan Eric, Romin Yevgeniy, Barlas Afsar, Chang Qing, Pancholi Priya, Timaul Neilawattie Merna, Overholtzer Michael, Yaeger Rona, Manova-Todorova Katia, de Stanchina Elisa, Bosenberg Marcus W, Rosen Neal
Abstract excerpt
BRAF V600E mutations occur in 46% of melanomas and drive high levels of ERK activity and ERK-dependent proliferation. However, BRAFV600E is insufficient to drive melanoma in genetically engineered mouse models, and 82% of human benign nevi harbor BRAFV600E mutations. We found that BRAFV600E inhibited mesenchymal migration by causing feedback inhibition of RAC1 activity. ERK pathway inhibition induced RAC1...
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