SPRED2 and hepatocellular carcinoma: In the present study, we aimed to determine the biological significance of endogenous SPRED2 regarding the fate of HCC cells and demonstrate, for the first time, that the loss of endogenous SPRED2 results in increased epithelial–mesenchymal transition (EMT) and stemness, two potentially linked cellular states [26,27], in HCC cells via the upregulation of ERK1/2 and its downstream signaling pathways.