MAPK1 and hepatocellular carcinoma: In addition, activation of Ras/Raf/MEK/ERK pathway in HCC may be due to down-regulation of Ras inhibitors Sprouty and the Sprouty-related protein with Ena/vasodilator-stimulated phosphoprotein homology-1 domain (Spred-1) and Spred-2 proteins [92, 93].