title: Down-regulation of β-arrestin2 promotes tumour invasion and indicates poor prognosis of hepatocellular carcinoma.
abstract: β-arrestins, including β-arrestin1 and β-arrestin2, are multifunctional adaptor proteins. β-arrestins have recently been found to play new roles in regulating intracellular signalling networks associated with malignant cell functions. Altered β-arrestin expression has been reported in many cancers, but its role in hepatocellular carcinoma (HCC) is not clear. We therefore examined the roles of β-arrestins in HCC using an animal model of progressive HCC, HCC patient samples and HCC cell lines with stepwise metastatic potential. We demonstrated that β-arrestin2 level, but not β-arrestin1 level, decreased in conjunction with liver tumourigenesis in a mouse diethylnitrosamine-induced liver tumour model. Furthermore, β-arrestin2 expression was reduced in HCC tissues compared with noncancerous tissues in HCC patients. β-arrestin2 down-regulation in HCC was significantly associated with poor patient prognoses and aggressive pathologic features. In addition, our in vitro study showed that β-arrestin2 overexpression significantly reduced cell migration and invasion in cultured HCC cells. Furthermore, β-arrestin2 overexpression up-regulated E-cadherin expression and inhibited vimentin expression and Akt activation. These results suggest that β-arrestin2 down-regulation increases HCC cell migration and invasion ability. Low β-arrestin2 expression may be indicative of a poor prognosis or early cancer recurrence in patients who have undergone surgery for HCC.
authors.affiliation: Institute of Clinical Pharmacology of Anhui Medical University, Hefei 230032, China.|Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei 230032, China.|Anhui Collaborative Innovation Center of Anti-Inflammatory and Immune Medicine, Hefei, 230032, China.
authors.forename: Wu-Yi
authors.initials: WY
authors.lastname: Sun
authors.affiliation: Institute of Clinical Pharmacology of Anhui Medical University, Hefei 230032, China.|Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei 230032, China.|Anhui Collaborative Innovation Center of Anti-Inflammatory and Immune Medicine, Hefei, 230032, China.
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Hu
authors.affiliation: Institute of Clinical Pharmacology of Anhui Medical University, Hefei 230032, China.|Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei 230032, China.|Anhui Collaborative Innovation Center of Anti-Inflammatory and Immune Medicine, Hefei, 230032, China.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Wu
authors.affiliation: Institute of Clinical Pharmacology of Anhui Medical University, Hefei 230032, China.|Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei 230032, China.|Anhui Collaborative Innovation Center of Anti-Inflammatory and Immune Medicine, Hefei, 230032, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Institute of Clinical Pharmacology of Anhui Medical University, Hefei 230032, China.|Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei 230032, China.|Anhui Collaborative Innovation Center of Anti-Inflammatory and Immune Medicine, Hefei, 230032, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Institute of Clinical Pharmacology of Anhui Medical University, Hefei 230032, China.|Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei 230032, China.|Anhui Collaborative Innovation Center of Anti-Inflammatory and Immune Medicine, Hefei, 230032, China.
authors.forename: Qing-Tong
authors.initials: QT
authors.lastname: Wang
authors.affiliation: Institute of Clinical Pharmacology of Anhui Medical University, Hefei 230032, China.|Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei 230032, China.|Anhui Collaborative Innovation Center of Anti-Inflammatory and Immune Medicine, Hefei, 230032, China.
authors.forename: Jing-Yu
authors.initials: JY
authors.lastname: Chen
authors.affiliation: Institute of Clinical Pharmacology of Anhui Medical University, Hefei 230032, China.|Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei 230032, China.|Anhui Collaborative Innovation Center of Anti-Inflammatory and Immune Medicine, Hefei, 230032, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
mesh_terms: D000818:Animals; D063646:Carcinogenesis; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D004052:Diethylnitrosamine; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D000071560:beta-Arrestin 2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000071560:beta-Arrestin 2; D004052:Diethylnitrosamine