Article
Ligand-independent EPHA2 signaling drives the adoption of a targeted therapy-mediated metastatic melanoma phenotype.
Cancer discovery - 1 Mar 2015
Paraiso Kim H T, Das Thakur Meghna, Fang Bin, Koomen John M, Fedorenko Inna V, John Jobin K, Tsao Hensin, Flaherty Keith T, Sondak Vernon K, Messina Jane L, Pasquale Elena B, Villagra Alejandro, Rao Uma N, Kirkwood John M, Meier Friedegund, Sloot Sarah, Gibney Geoffrey T, Stuart Darrin, Tawbi Hussein, Smalley Keiran S M
Abstract excerpt
UNLABELLED: Many patients with BRAF inhibitor resistance can develop disease at new sites, suggesting that drug-induced selection pressure drives metastasis. Here, we used mass spectrometry-based phosphoproteomic screening to uncover ligand-independent EPHA2 signaling as an adaptation to BRAF inhibitor therapy that led to the adoption of a metastatic phenotype. The EPHA2-mediated invasion was AKT-dependent and...
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