Tumor Biology

, Volume 33, Issue 5, pp 1745–1758 | Cite as

CCN1 promotes tumorigenicity through Rac1/Akt/NF-κB signaling pathway in pancreatic cancer

  • Xuqing Wang
  • Yuezhen Deng
  • Zhengfa Mao
  • Xiaoyan Ma
  • Xin Fan
  • Lei Cui
  • Jianguo Qu
  • Dong Xie
  • Jianxin Zhang
Research Article

Abstract

Aberrant CCN1 expression has been reported to play an important role in the tumor development. However, the pattern and the role of CCN1 in pancreatic cancer remain largely unknown. Therefore, we further deciphered the role CCN1 played in pancreatic cancer. We first evaluated the CCN1 expression in human pancreatic cancer tissues and pancreatic cancer cells. Then we forced expression and silenced CCN1 expression in pancreatic cancer cell lines MIA PaCa2 and PANC-1 respectively, using lentivirus vectors. We characterized the stable cells in vitro and in vivo using a nude mouse xenograft model. In this study, we found that CCN1 expression was significantly higher in cancer specimens which positively correlated with the expression level of phosphorylated Akt and p65. and poorer outcome. Moreover, our results demonstrated that CCN1 positively regulated pancreatic cell growth in vitro and in vivo and helped cancer cells resist to tumor necrosis factor alpha-induced apoptosis. Furthermore, we disclosed that activation of CCN1/ras-related c3 botulinum toxin substrate 1 (Rac1)/V-akt murine thymoma viral oncogene homolog (Akt)/nuclear factor-kappa B pathway inhibited apoptosis in pancreatic cancer cells. CCN1 is upregulated in pancreatic cancer and promotes the survival of pancreatic cancer cells. Taken together, these results indicate that CCN1 may be a potential target for pancreatic cancer therapy.

Keywords

CCN1 Pancreatic ductal adenocarcinoma Apoptosis NF-κB pathway 

Notes

Acknowledgments

This work was sponsored by the National Natural Science Foundation of China, grant number 81070287 and Zhenjiang Science and Technology Pillar Program, grant numbers SH2009013 and SH2011026.

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2012

Authors and Affiliations

  • Xuqing Wang
    • 1
  • Yuezhen Deng
    • 2
  • Zhengfa Mao
    • 1
  • Xiaoyan Ma
    • 1
  • Xin Fan
    • 1
  • Lei Cui
    • 3
  • Jianguo Qu
    • 1
  • Dong Xie
    • 2
  • Jianxin Zhang
    • 1
  1. 1.Department of General SurgeryAffiliated Hospital of Jiangsu UniversityZhenjiangPeople’s Republic of China
  2. 2.Laboratory of Molecular OncologyInstitute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of SciencesShanghaiPeople’s Republic of China
  3. 3.Department of General Surgery, Zhongshan HospitalFudan UniversityShanghaiPeople’s Republic of China

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