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Tumor Biology

, Volume 34, Issue 5, pp 2835–2842 | Cite as

Ataxia–telangiectasia group D complementing gene (ATDC) upregulates matrix metalloproteinase 9 (MMP-9) to promote lung cancer cell invasion by activating ERK and JNK pathways

  • Zhong-Ping Tang
  • Quan-Zhe Cui
  • Qian-Ze Dong
  • Ke Xu
  • En-Hua Wang
Research Article

Abstract

Although the expression pattern and biological functions of ataxia–telangiectasia group D complementing gene (ATDC) had been implicated in several types of cancer, the roles and potential mechanisms of ATDC in lung cancer cell invasion are still ambiguous. In this study, we used gain- and loss-of-function analyses to explore the roles and potential mechanisms of ATDC in lung cancer cell invasion. siRNA knockdown of ATDC impaired cell invasion in A549 and H1299 cell lines, and its overexpression promoted cell invasion in HBE cell line. ATDC may contribute to the invasive ability of lung cancer cells by promoting the expression of invasion-related matrix metalloproteinase 9 (MMP-9). In addition, ATDC increased activating protein 1 (AP-1) reporter luciferase activity and the protein and mRNA levels of c-Jun and c-Fos. We further demonstrated that the roles of ATDC on cell invasion, MMP-9 upregulation, and AP-1 activation were dependent on extracellular signal-regulated protein kinase (ERK) and c-Jun N-terminal kinase (JNK) pathway activation, and ERK inhibitor U0126 or JNK inhibitor SP600125 blocked these effects of ATDC. These results suggested that ATDC upregulates MMP-9 to promote lung cancer cell invasion by activating ERK and JNK pathways.

Keywords

ATDC TRIM29 MMP-9 AP-1 ERK JNK 

Notes

Acknowledgments

This study was supported by the National Natural Science Foundation of China (NSFC nos. 81071905, 81272606).

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • Zhong-Ping Tang
    • 1
  • Quan-Zhe Cui
    • 1
  • Qian-Ze Dong
    • 1
  • Ke Xu
    • 2
  • En-Hua Wang
    • 1
  1. 1.Department of Pathology, the First Affiliated Hospital and College of Basic Medical SciencesChina Medical UniversityShenyangChina
  2. 2.Department of Radiology, the First Affiliated HospitalChina Medical UniversityShenyangChina

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