HSPG2 and liver cancer: Indeed, treatment of PLC liver cancer cells in vitro with a Shp2 inhibitor (SHP099) or Mek inhibitor (Trametinib), or a Shp2-targeting CRISPR vector, also upregulated CD133 expression (Figure 4D, E), indicating that CD133 induction is an inherent cellular response to impaired signaling of the RTK-Ras-Erk pathway.