title: The asialoglycoprotein receptor suppresses the metastasis of hepatocellular carcinoma via LASS2-mediated inhibition of V-ATPase activity.
abstract: The asialoglycoprotein receptor (ASGR), which is expressed mainly in hepatocytes, is downregulated in poorly differentiated hepatocellular carcinoma (HCC). Here we investigated the role of ASGR1 in HCC metastasis as well as the possible underlying molecular mechanisms. We found that ASGR1 was downregulated in HCC tissue compared with adjacent non-tumorous liver tissue and that lower ASGR1 expression was associated with higher TNM stage and poorer prognosis in HCC patients. ASGR1 overexpression inhibited hepatoma cell migration and invasion in vitro and in vivo, while ASGR1 knockdown had the opposite effects. Furthermore, ASGR1 interacted directly with human longevity assurance homolog 2 of yeast LAG1 (LASS2). Knockdown of LASS2 attenuated the inhibitory effects of ASGR1 on hepatoma cell migration and invasion in vitro. ASGR1 decreased V-ATPase activity in hepatoma cells, and this was reversed by LASS2 knockdown. Finally, HCC patients with low LASS2 levels had poor prognosis, while those with high ASGR1 and LASS2 levels had better prognosis. Thus, ASGR1 may act as a potential metastasis suppressor in HCC, and the combination of ASGR1 and LASS2 may help predict the prognosis of HCC patients.
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, No. 25/Ln 2200 Xie-Tu Road, Shanghai 200032, China; Department of Pathophysiology, Guangdong Medical College, Dongguan 523808, Guangdong, China.
authors.forename: Dishui
authors.initials: D
authors.lastname: Gu
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, No. 25/Ln 2200 Xie-Tu Road, Shanghai 200032, China.
authors.forename: Haojie
authors.initials: H
authors.lastname: Jin
authors.affiliation: Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
authors.forename: Guangzhi
authors.initials: G
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, No. 25/Ln 2200 Xie-Tu Road, Shanghai 200032, China.
authors.forename: Cun
authors.initials: C
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, No. 25/Ln 2200 Xie-Tu Road, Shanghai 200032, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, No. 25/Ln 2200 Xie-Tu Road, Shanghai 200032, China.
authors.forename: Fangyuan
authors.initials: F
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, No. 25/Ln 2200 Xie-Tu Road, Shanghai 200032, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, No. 25/Ln 2200 Xie-Tu Road, Shanghai 200032, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chu
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, No. 25/Ln 2200 Xie-Tu Road, Shanghai 200032, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yao
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, No. 25/Ln 2200 Xie-Tu Road, Shanghai 200032, China. Electronic address: wxqin@sjtu.edu.cn.
authors.forename: Wenxin
authors.initials: W
authors.lastname: Qin
mesh_terms: D000818:Animals; D037263:Asialoglycoprotein Receptor / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000235:genetics / Q000556:secondary / Q000628:therapy; D002465:Cell Movement; D056945:Hep G2 Cells; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000517:prevention & control / Q000556:secondary; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D034622:RNA Interference; D015398:Signal Transduction; D051049:Sphingosine N-Acyltransferase / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism*
chemical_list: C546927:ASGR1 protein, human; D037263:Asialoglycoprotein Receptor; D008565:Membrane Proteins; D025521:Tumor Suppressor Proteins; C438311:CERS2 protein, human; D051049:Sphingosine N-Acyltransferase; D025262:Vacuolar Proton-Translocating ATPases
keywords: ASGR; Cancer metastasis; Hepatocellular carcinoma; LASS2; V-ATPase