Down-regulation of β-arrestin2 promotes tumour invasion and indicates poor prognosis of hepatocellular carcinoma

beta-arrestins, including beta-arrestin1 and beta-arrestin2, are multifunctional adaptor proteins. beta-arrestins have recently been found to play new roles in regulating intracellular signalling networks associated with malignant cell functions. Altered beta-arrestin expression has been reported in many cancers, but its role in hepatocellular carcinoma ( HCC) is not clear. We therefore examined the roles of beta-arrestins in HCC using an animal model of progressive HCC, HCC patient samples and HCC cell lines with stepwise metastatic potential. We demonstrated that beta-arrestin2 level, but not beta-arrestin1 level, decreased in conjunction with liver tumourigenesis in a mouse diethylnitrosamine-induced liver tumour model. Furthermore, beta-arrestin2 expression was reduced in HCC tissues compared with noncancerous tissues in HCC patients. beta-arrestin2 down-regulation in HCC was significantly associated with poor patient prognoses and aggressive pathologic features. In addition, our in vitro study showed that beta-arrestin2 overexpression significantly reduced cell migration and invasion in cultured HCC cells. Furthermore, beta-arrestin2 overexpression up-regulated E-cadherin expression and inhibited vimentin expression and Akt activation. These results suggest that beta-arrestin2 down-regulation increases HCC cell migration and invasion ability. Low beta-arrestin2 expression may be indicative of a poor prognosis or early cancer recurrence in patients who have undergone surgery for HCC.