Journal of Cancer Research and Clinical Oncology

, Volume 141, Issue 6, pp 1037–1047 | Cite as

NAIF1 inhibits gastric cancer cells migration and invasion via the MAPK pathways

  • Mei Yang
  • Yu-yu Gu
  • Hua Peng
  • Mei Zhao
  • Jia Wang
  • Sheng-kai Huang
  • Xing-hua Yuan
  • Jia Li
  • Jian-li Sang
  • Qing Luo
  • Changzhi Huang
Original Article – Cancer Research
First Online:
Received:
Accepted:

Abstract

Purpose

Nuclear apoptosis-inducing factor 1 (NAIF1) could induce apoptosis in gastric cancer cells. Previously, we have reported that the expression of NAIF1 protein is down-regulated in gastric cancer tissues compared with the adjacent normal tissues. However, the role of NAIF1 in gastric cancer cells is not fully understood.

Methods

The effects of NAIF1 on cell viability were evaluated by MTT and colony formation assays. The ability of cellular migration and invasion were analyzed by transwell assays. The expression levels of targeted proteins were determined by western blot. The relative RNA expression levels were analyzed using quantitative polymerase chain reaction assays. Xenograft experiment was employed to determine the anti-tumor ability of NAIF1 in vivo.

Results

The study demonstrates that transient transfection of NAIF1 in gastric cancer cells BGC823 and MKN45 could inhibit the cell proliferation, migration, and invasion of the two gastric cancer cell lines. The tumor size is smaller in NAIF1-overexpressed MKN45 cell xenograft mice than in unexpressed group. Further in-depth analysis reveals that NAIF1 reduces the expression of MMP2 as well as MMP9, and inhibits the activation of FAK, all of which are key molecules involved in regulating cell migration and invasion. In addition, NAIF1 inhibits the expression of c-Jun N-terminal kinase (JNK) by accelerating its degradation through ubiquitin–proteasome pathway. Meanwhile, NAIF1 reduces the mRNA and protein expression of ERK1/2.

Conclusions

Our study revealed that NAIF1 plays a role in regulating cellular migration and invasion through the MAPK pathways. It could be a therapeutic target for gastric cancer.

Keywords

NAIF1 Gastric cancer Migration Invasion MAPK 
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Notes

Acknowledgments

The project was supported by Open Fund of Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Beijing Normal University (201301). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Conflict of interest

We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work and that there is no professional or other personal interest of any nature or kind in any product, service, and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled, “NAIF1 Inhibits Gastric Cancer Cells Migration and Invasion via the MAPK Pathways”.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Mei Yang
    • 1
  • Yu-yu Gu
    • 1
  • Hua Peng
    • 1
  • Mei Zhao
    • 1
  • Jia Wang
    • 1
  • Sheng-kai Huang
    • 1
  • Xing-hua Yuan
    • 2
  • Jia Li
    • 3
  • Jian-li Sang
    • 4
  • Qing Luo
    • 5
  • Changzhi Huang
    • 1
  1. 1.Department of Etiology and Carcinogenesis and State Key Laboratory of Molecular Oncology, Cancer Institute and HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingPeople’s Republic of China
  2. 2.Department of Abdomen Surgery, Cancer Institute and HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingPeople’s Republic of China
  3. 3.Department of Clinical Laboratory, Cancer Institute and HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingPeople’s Republic of China
  4. 4.Institute of Cell Biology, College of Life SciencesBeijing Normal UniversityBeijingPeople’s Republic of China
  5. 5.Affiliated Hospital of Zunyi Medical CollegeZunyiPeople’s Republic of China

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