The importance of the RAS/RAF/MAPK cascade in regulating cellular proliferation, differentiation and survival is highlighted by the fact that components of the pathway are mutated with high frequency in a large number of human cancers. Activating mutations in RAS are found in approximately one third of human cancers, while ~8% of tumors express an activated form of BRAF. RAS pathway activation is also achieved in a smaller subset of cancers by loss-of-function mutations in negative regulators of RAS signaling, such as the RAS GAP NF1(reviewed in Prior et al, 2012; Pylayeva-Gupta et al, 2011; Stephen et al, 2014; Lavoie and Therrien, 2015; Lito et al, 2013; Samatar and Poulikakos, 2014; Maertens and Cichowski, 2014).
Lavoie, H, Therrien, M
Grabocka, E, Pylayeva-Gupta, Y, Bar-Sagi, D
Cichowski, K, Maertens, O
Lito, P, Solit, DB, Rosen, N
Lewis, PD, Mattos, C, Prior, IA
Poulikakos, PI, Samatar, AA
McCormick, F, Stephen, AG, Bagni, RK, Esposito, D
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