To explore whether the SUMO-site mutation of Shp2K590R affects the ERK signaling and tumorigenesis of human hepatocellular carcinoma cell lines, firstly we knocked down endogenous Shp2 in HepG2 and SMMC-7721 cells by shRNA for 3′-UTR of Shp2 mRNA, and then stably re-expressing the lenti-vector, Shp2WT or Shp2K590R in these cells by lentiviral system as described before [12], and the expression levels of Shp2 were assessed comparable by Western blotting. Here, PTPN11 is linked to hepatocellular carcinoma.