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Metadherin confers chemoresistance of cervical cancer cells by inducing autophagy and activating ERK/NF-κB pathway

Tumor Biology volume 34, pages 2433–2440 (2013)Cite this article

Abstract

Overexpression of metadherin (MTDH) has been reported in many solid tumors and implicated in chemoresistance. This study aimed to examine MTDH expression in cervical cancer tissues and explore its role in chemoresistance of cervical cancer. MTDH expression in cervical cancer biopsies and several cervical cancer cell lines was detected by immunoblotting and immunohistochemisty. MTDH expression level was experimentally modulated in HeLa cells to determine the effects on chemoresistance to cisplatin. The results showed that MTDH expression was higher in tissues from both cervical squamous carcinoma and cervical adenocarcinoma, compared to normal cervical tissues. MTDH expression was not correlated to patient age or cervical cancer grade, although nuclear MTDH expression was correlated with poor differentiation of cervical cancer. In SiHa, HeLa, CasKi, and C33A cells, MTDH expression level was positively correlated with chemoresistance to cisplatin. MTDH increased autophagy in HeLa cells, which was associated with decreased cleavage of Caspase-3 and the activation of EER/NF-κB pathway. In conclusion, MTDH expression is high in cervical cancer, and it contributes to chemoresistance of cervical cancer. MTDH could be utilized as a therapeutic target to overcome chemoresistance of cervical cancer.

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Acknowledgments

We thank Prof. Xiangbing Meng for the MTDH plasmid, empty plasmid, MTDH shRNA, and control non-silencing shRNA plasmids. This study was supported by grants from the National Natural Science Foundation of China (nos. 30901706, 81000726, and 81101235), the Natural Science Foundation of Heilongjiang Province (nos. ZD201020 and D200946), and the Key Project of Chinese Ministry of Education(no. 212043)

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Affiliations

  1. Department of Microbiology, Immunity and Infection, Pathogenic Biology Key Laboratory, Harbin Medical University, Heilongjiang Province, Harbin, 150081, China

    Jingwei Zhang, Shuang Liu, Qingmeng Zhang, Yan Wang, Liping Tong, Xiaohang Chen, Yuting Ji, Qinglong Shang & Lanlan Wei

  2. Department of Gynecology, The Third Affiliated Hospital, Harbin Medical University, Harbin, 150081, China

    Yunyan Zhang

  3. Department of Neurosurgery, The First Affiliated Hospital, Harbin Medical University, Harbin, 150001, China

    Baozhan Xu & Ming Chu

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  1. Jingwei Zhang
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  2. Yunyan Zhang
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  3. Shuang Liu
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  4. Qingmeng Zhang
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  5. Yan Wang
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  11. Ming Chu
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  12. Lanlan Wei
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Correspondence to Ming Chu or Lanlan Wei.

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Zhang, J., Zhang, Y., Liu, S. et al. Metadherin confers chemoresistance of cervical cancer cells by inducing autophagy and activating ERK/NF-κB pathway. Tumor Biol. 34, 2433–2440 (2013). https://doi.org/10.1007/s13277-013-0794-z

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  • DOI: https://doi.org/10.1007/s13277-013-0794-z

Keywords

  • Metadherin
  • Cervical cancer
  • Chemoresistance
  • Cisplatin
  • Autophagy