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Axl gene knockdown inhibits the metastasis properties of hepatocellular carcinoma via PI3K/Akt-PAK1 signal pathway

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Tumor Biology

Abstract

The objective of this study is to clarify the possible role and mechanism of Axl in the tumorigenicity and metastasis process of hepatocellular carcinoma. The mRNA and protein expression levels of Axl in MHCC97-H and MHCC97-L cell lines were evaluated by real-time PCR and Western blot analysis. The key factor of phosphatidylinositol-3-kinase (PI3K)/Akt-p21-activated kinases-1 (PAK1) signaling pathway was studied after Axl expression was downregulated by shRNA. Finally, we analyzed the expression status of Axl protein expression in hepatocellular carcinoma tissues and its relationship with the prognosis of hepatocellular carcinoma. Axl was observed to be higher expressed in MHCC97-H cell lines compared to MHCC97-L cell lines. The downregulation of Axl in MHCC97-H cell lines resulted in the inhibition of the invasion ability of MHCC97-H cells both in vitro and in vivo. Interestingly, blocking PI3K/Akt signaling pathway by LY294002 or Akt siRNA could remarkably inhibit the PAK1 activation and cell invasion. Finally, the Axl protein expression was positively correlated with differentiation, lymph node metastasis, and clinical stage in patients with hepatocellular carcinoma patients (all P < 0.01). These findings suggest that Axl can also regulate the metastasis process of hepatocellular carcinoma and may serve as a new prognostic marker and therapeutic target for treating hepatocellular carcinoma metastasis.

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Acknowledgments

This work was supported by a grant from The National Natural Science Foundation of China director fund (81250025).

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Authors and Affiliations

  1. Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, 116027, Liaoning Province, China

    Jingchao Xu, Zhenhai Ma & Yongfu Zhao

  2. College of Laboratory Medicine, Dalian Medical University, Dalian, 116044, Liaoning Province, China

    Li Jia, Hongye Ma & Yanping Li

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  1. Jingchao Xu
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  2. Li Jia
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  3. Hongye Ma
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  4. Yanping Li
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  5. Zhenhai Ma
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  6. Yongfu Zhao
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Correspondence to Yongfu Zhao.

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Xu, J., Jia, L., Ma, H. et al. Axl gene knockdown inhibits the metastasis properties of hepatocellular carcinoma via PI3K/Akt-PAK1 signal pathway. Tumor Biol. 35, 3809–3817 (2014). https://doi.org/10.1007/s13277-013-1521-5

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  • DOI: https://doi.org/10.1007/s13277-013-1521-5

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