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Article

Overexpression of Yes-associated protein confers doxorubicin resistance in hepatocellullar carcinoma

  • Authors:
    • Xinying Huo
    • Qi Zhang
    • Angela M. Liu
    • Cuiju Tang
    • Yongling Gong
    • Jianmin Bian
    • John M. Luk
    • Zhi Xu
    • Jinfei Chen
  • View Affiliations / Copyright

    Affiliations: Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, P.R. China, Departments of Pharmacology and Surgery, National University of Singapore, 117597 Singapore, Republic of Singapore, Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, P.R. China
  • Pages: 840-846
    |
    Published online on: December 10, 2012
       https://doi.org/10.3892/or.2012.2176
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Abstract

Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies worldwide and is highly resistant to chemotherapy. Yes-associated protein (YAP) is the downstream effector of the Hippo signaling pathway, which is frequently overexpressed in many types of cancers. Amplification of the YAP gene and overexpression of YAP in HCC have previously been reported to contribute to hepatocyte malignant transformation and tumor progression. In this study, we aimed to investigate the potential role of YAP in HCC chemoresistance. Overexpression of YAP resulted in resistance against doxorubicin-induced apoptosis in HCC cell lines, whereas suppression of the endogenous YAP expression by RNA interference demonstrated the reverse effect. Western blotting revealed that, following exposure to doxorubicin, YAP-overexpressing cells exhibited decreased cleaved PARP, increased phosphorylation of Akt and ERK1/2, and elevated Bcl-xL expression in comparison to the vector control. Inhibition of YAP expression sensitized HCC cells to doxorubicin, by exhibiting increased cleaved PARP, decreased levels of phosphorylated Akt, phosphorylated ERK1/2 and Bcl-xL expression. In addition, pretreatment with the MEK1/2 inhibitor U0126 but not the PI3-K inhibitor LY294002 significantly enhanced doxorubicin-induced apoptosis and decreased Bcl-xL expression in YAP-overexpressing HCC cells. Our data provide evidence that overexpression of YAP plays an important role in conferring doxorubicin resistance to HCC, which is at least partially mediated by YAP-induced activation of the MAP kinase pathway. Targeting YAP may be a promising adjunct for overcoming doxorubicin resistance in HCC.
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Copy and paste a formatted citation
Spandidos Publications style
Huo X, Zhang Q, Liu AM, Tang C, Gong Y, Bian J, Luk JM, Xu Z and Chen J: Overexpression of Yes-associated protein confers doxorubicin resistance in hepatocellullar carcinoma. Oncol Rep 29: 840-846, 2013.
APA
Huo, X., Zhang, Q., Liu, A.M., Tang, C., Gong, Y., Bian, J. ... Chen, J. (2013). Overexpression of Yes-associated protein confers doxorubicin resistance in hepatocellullar carcinoma. Oncology Reports, 29, 840-846. https://doi.org/10.3892/or.2012.2176
MLA
Huo, X., Zhang, Q., Liu, A. M., Tang, C., Gong, Y., Bian, J., Luk, J. M., Xu, Z., Chen, J."Overexpression of Yes-associated protein confers doxorubicin resistance in hepatocellullar carcinoma". Oncology Reports 29.2 (2013): 840-846.
Chicago
Huo, X., Zhang, Q., Liu, A. M., Tang, C., Gong, Y., Bian, J., Luk, J. M., Xu, Z., Chen, J."Overexpression of Yes-associated protein confers doxorubicin resistance in hepatocellullar carcinoma". Oncology Reports 29, no. 2 (2013): 840-846. https://doi.org/10.3892/or.2012.2176
Copy and paste a formatted citation
x
Spandidos Publications style
Huo X, Zhang Q, Liu AM, Tang C, Gong Y, Bian J, Luk JM, Xu Z and Chen J: Overexpression of Yes-associated protein confers doxorubicin resistance in hepatocellullar carcinoma. Oncol Rep 29: 840-846, 2013.
APA
Huo, X., Zhang, Q., Liu, A.M., Tang, C., Gong, Y., Bian, J. ... Chen, J. (2013). Overexpression of Yes-associated protein confers doxorubicin resistance in hepatocellullar carcinoma. Oncology Reports, 29, 840-846. https://doi.org/10.3892/or.2012.2176
MLA
Huo, X., Zhang, Q., Liu, A. M., Tang, C., Gong, Y., Bian, J., Luk, J. M., Xu, Z., Chen, J."Overexpression of Yes-associated protein confers doxorubicin resistance in hepatocellullar carcinoma". Oncology Reports 29.2 (2013): 840-846.
Chicago
Huo, X., Zhang, Q., Liu, A. M., Tang, C., Gong, Y., Bian, J., Luk, J. M., Xu, Z., Chen, J."Overexpression of Yes-associated protein confers doxorubicin resistance in hepatocellullar carcinoma". Oncology Reports 29, no. 2 (2013): 840-846. https://doi.org/10.3892/or.2012.2176
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