Downregulation of JWA promotes tumor invasion and predicts poor prognosis in human hepatocellular carcinoma

Authors

  • Xiaofeng Wu,

    1. Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, People's Republic of, China
    Search for more papers by this author
  • Hairong Chen,

    1. Department of Molecular Cell Biology and Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu Province, People's Republic of, China
    Search for more papers by this author
  • Qiang Gao,

    1. Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of, China
    2. Key Laboratory for Carcinogenesis and Cancer Invasion, The Chinese Ministry of Education, Shanghai, People's Republic of, China
    Search for more papers by this author
  • Jin Bai,

    1. Department of Molecular Cell Biology and Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu Province, People's Republic of, China
    Search for more papers by this author
  • Xiaoying Wang,

    1. Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of, China
    2. Key Laboratory for Carcinogenesis and Cancer Invasion, The Chinese Ministry of Education, Shanghai, People's Republic of, China
    Search for more papers by this author
  • Jian Zhou,

    1. Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of, China
    2. Key Laboratory for Carcinogenesis and Cancer Invasion, The Chinese Ministry of Education, Shanghai, People's Republic of, China
    Search for more papers by this author
  • Shuangjian Qiu,

    1. Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of, China
    2. Key Laboratory for Carcinogenesis and Cancer Invasion, The Chinese Ministry of Education, Shanghai, People's Republic of, China
    Search for more papers by this author
  • Yang Xu,

    1. Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of, China
    2. Key Laboratory for Carcinogenesis and Cancer Invasion, The Chinese Ministry of Education, Shanghai, People's Republic of, China
    Search for more papers by this author
  • Yinghong Shi,

    1. Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of, China
    2. Key Laboratory for Carcinogenesis and Cancer Invasion, The Chinese Ministry of Education, Shanghai, People's Republic of, China
    Search for more papers by this author
  • Xuehao Wang,

    1. Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, People's Republic of, China
    Search for more papers by this author
  • Jianwei Zhou,

    Corresponding author
    1. Department of Molecular Cell Biology and Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu Province, People's Republic of, China
    • Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical School, Fudan University, 180 FengLin Road, Shanghai 200032, China.

      Department of Molecular Cell Biology and Toxicology, School of Public Health, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, China.

    Search for more papers by this author
  • Jia Fan

    Corresponding author
    1. Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of, China
    2. Key Laboratory for Carcinogenesis and Cancer Invasion, The Chinese Ministry of Education, Shanghai, People's Republic of, China
    • Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical School, Fudan University, 180 FengLin Road, Shanghai 200032, China.

      Department of Molecular Cell Biology and Toxicology, School of Public Health, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, China.

    Search for more papers by this author

  • The authors have no conflict of interest.
  • Xiaofeng Wu and Hairong Chen contributed equally to this work.

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. © 2012 Wiley Periodicals, Inc.

Ancillary