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

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• 作者：Jingwei Zhang (1)
  Yunyan Zhang (2)
  Shuang Liu (1)
  Qingmeng Zhang (1)
  Yan Wang (1)
  Liping Tong (1)
  Xiaohang Chen (1)
  Yuting Ji (1)
  Qinglong Shang (1)
  Baozhan Xu (3)
  Ming Chu (3)
  Lanlan Wei (1)
  
• 关键词：Metadherin ; Cervical cancer ; Chemoresistance ; Cisplatin ; Autophagy
• 刊名：Tumor Biology
• 出版年：2013
• 出版时间：August 2013
• 年：2013
• 卷：34
• 期：4
• 页码：2433-2440
• 全文大小：758KB
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• 作者单位：Jingwei Zhang (1)
  Yunyan Zhang (2)
  Shuang Liu (1)
  Qingmeng Zhang (1)
  Yan Wang (1)
  Liping Tong (1)
  Xiaohang Chen (1)
  Yuting Ji (1)
  Qinglong Shang (1)
  Baozhan Xu (3)
  Ming Chu (3)
  Lanlan Wei (1)
  
  1. Department of Microbiology, Immunity and Infection, Pathogenic Biology Key Laboratory, Harbin Medical University, Heilongjiang Province, Harbin, 150081, China
  2. Department of Gynecology, The Third Affiliated Hospital, Harbin Medical University, Harbin, 150081, China
  3. Department of Neurosurgery, The First Affiliated Hospital, Harbin Medical University, Harbin, 150001, China
  
• ISSN：1423-0380

文摘

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.