27 The colocalization and interaction of PAK1 with CIB1 were also demonstrated in two HCC cell lines (Fig. S4d-e). Thus, we wondered whether the CIB1/PAK1 complex functions as a mediator of MAPK pathway facilitation and a protective mechanism for the survival of HCC cells upon exposure to lenvatinib. Indeed, facilitation of the MEK1/2-ERK1/2 cascade is elicited by knockdown of USP14 in two HCC cell lines, as determined by decreases in p-MEK1/2 and p-ERK1/2, while overexpression of CIB1 rescued this process (Fig. 4g; Fig. S4f). Here, USP14 is linked to hepatocellular carcinoma.