title: Downregulation of JWA promotes tumor invasion and predicts poor prognosis in human hepatocellular carcinoma.
abstract: We previously identified JWA as a novel microtubule-associated protein (MAP), which is implicated in carcinogenesis and tumor progression. The aims of the present study were to investigate the biological action and the prognostic significance of JWA in hepatocellular carcinoma (HCC). Quantitative real-time PCR and Western blot were used to detect JWA mRNA and protein expression, respectively, in stepwise metastatic HCC cell lines and HCC tissues. Short hairpin RNA was used to inhibit JWA expression in HCC cells. The effects of JWA depletion on cell migration, invasion, adhesion and in vivo metastasis were investigated. Immunohistochemistry of JWA was conducted in microarrays with tissue from 314 HCC patients who had undergone surgical resection. Prognostic significance was assessed using the Kaplan-Meier method and log-rank tests. The result showed JWA expression was decreased in the highly metastatic HCC cell lines and HCC tissues. Depletion of JWA caused a notable increase in cell migration, invasion and adhesion in vitro and metastasis in vivo. Furthermore, there was an inverse correlation between JWA expression and FAK expression and phosphorylation, RhoA activation and matrix metalloproteinase-2 (MMP-2) activity in HCC cells. More notably, multivariate analysis revealed that a low level of JWA expression was an independent prognosticator for both recurrence-free and overall survival for HCC patients after surgical resection, especially for AFP-normal HCC patients. Taken together, our data demonstrate that JWA plays a crucial role in HCC progression and suggest JWA may be a potential prognostic biomarker and therapeutic target for HCC.
authors.affiliation: Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, People's Republic of, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Wu
authors.forename: Hairong
authors.initials: H
authors.lastname: Chen
authors.forename: Qiang
authors.initials: Q
authors.lastname: Gao
authors.forename: Jin
authors.initials: J
authors.lastname: Bai
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.forename: Shuangjian
authors.initials: S
authors.lastname: Qiu
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.forename: Yinghong
authors.initials: Y
authors.lastname: Shi
authors.forename: Xuehao
authors.initials: X
authors.lastname: Wang
authors.forename: Jianwei
authors.initials: J
authors.lastname: Zhou
authors.forename: Jia
authors.initials: J
authors.lastname: Fan
mesh_terms: D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000473:pathology*; D045744:Cell Line, Tumor; D017931:DNA Primers; D015536:Down-Regulation; D004789:Enzyme Activation; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008113:Liver Neoplasms / Q000201:enzymology / Q000473:pathology*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D026901:Membrane Transport Proteins; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D011379:Prognosis
chemical_list: C484566:ARL6IP5 protein, human; D014408:Biomarkers, Tumor; D017931:DNA Primers; D006360:Heat-Shock Proteins; D047908:Intracellular Signaling Peptides and Proteins; D026901:Membrane Transport Proteins; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020782:Matrix Metalloproteinases