Although we did not examine the interaction between SPRED2 and autophagic components in HCC cells, our finding that the inhibition of MAPK/ERK by PD98059 inhibited the activation of mTORC1 and subsequently activated autophagy in the absence of SPRED2 in SPRED2-KO cells strongly suggests the importance of MAPK/ERK in SPRED2-mediated autophagy in HCC cells. Here, MAPK1 is linked to hepatocellular carcinoma.