Kinase-Dead BRAF and Oncogenic RAS Cooperate to Drive Tumor Progression through CRAF

Heidorn, Sonja J.; Milagre, Carla; Whittaker, Steven R.; Nourry, Arnaud; Niculescu-Duvas, Ion; Dhomen, Nathalie; Hussain, Jahan; Reis‐Filho, Jorge S.; Springer, Caroline J.; Pritchard, Catrin; Marais, Richard

doi:10.1016/j.cell.2009.12.040

articleCellJan 1, 2010HYBRID OA

Kinase-Dead BRAF and Oncogenic RAS Cooperate to Drive Tumor Progression through CRAF

SJSonja J. Heidorn CMCarla Milagre SRSteven R. Whittaker ANArnaud Nourry INIon Niculescu-Duvas

Institute of Cancer Research · University of Leicester

PubMed

Indexed incrossrefpubmed

Abstract

We describe a mechanism of tumorigenesis mediated by kinase-dead BRAF in the presence of oncogenic RAS. We show that drugs that selectively inhibit BRAF drive RAS-dependent BRAF binding to CRAF, CRAF activation, and MEK-ERK signaling. This does not occur when oncogenic BRAF is inhibited, demonstrating that BRAF inhibition per se does not drive pathway activation; it only occurs when BRAF is inhibited in the presence of oncogenic RAS. Kinase-dead BRAF mimics the effects of the BRAF-selective drugs and kinase-dead Braf and oncogenic Ras cooperate to induce melanoma in mice. Our data reveal another paradigm of BRAF-mediated signaling that promotes tumor progression. They highlight the importance of understanding…

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1,464

total citations

FWCI: 70.50
Percentile: 100%
References: 39

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Topics & keywords

Topics

Keywords

Biology
Cancer research
MAPK/ERK pathway
Kinase
Carcinogenesis
Melanoma
Signal transduction
Anti-apoptotic Ras signalling cascade

UN Sustainable Development Goals

Good health and well-being

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