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

  • Research Article
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Tumor Biology

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.

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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.

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Authors and Affiliations

  1. Department of General Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, People’s Republic of China

    Xuqing Wang, Zhengfa Mao, Xiaoyan Ma, Xin Fan, Jianguo Qu & Jianxin Zhang

  2. Laboratory of Molecular Oncology, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People’s Republic of China

    Yuezhen Deng & Dong Xie

  3. Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China

    Lei Cui

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  1. Xuqing Wang
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Correspondence to Jianxin Zhang.

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Authors Xuqing Wang, Yuezhen Deng, Zhengfa Mao, and Xiaoyan Ma equally contributed to this work

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Wang, X., Deng, Y., Mao, Z. et al. CCN1 promotes tumorigenicity through Rac1/Akt/NF-κB signaling pathway in pancreatic cancer. Tumor Biol. 33, 1745–1758 (2012). https://doi.org/10.1007/s13277-012-0434-z

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  • DOI: https://doi.org/10.1007/s13277-012-0434-z

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