Tumor Biology

, Volume 36, Issue 8, pp 6053–6062 | Cite as

Activation of matrix metalloproteinase-9 (MMP-9) by neurotensin promotes cell invasion and migration through ERK pathway in gastric cancer

  • Hafeza Akter
  • Min Park
  • Oh-Seung Kwon
  • Eun Joo Song
  • Won-Sang Park
  • Min-Jung Kang
Research Article


Neurotensin (NT) is distributed throughout the brain and gastrointestinal tract. Although the relationship between NT and matrix metalloproteinase-9 (MMP-9) activity in gastric cancer has not been reported, the elevation of MMP-9 and NT is reported in the breast, lung, prostate, and gastric cancer. The aim of our study is to investigate the relationship between NT and MMP-9 activity and the underlying signaling mechanism in gastric cancer cell lines. Commercial ELISA kits were used for estimation of NT and MMP-9 expression, and fluorescence resonance energy transfer (FRET) assay was used for measurement of MMP-9 activity. Cell migration and invasion were determined by wound healing and transwell assay. The expression of signaling proteins was measured by Western blotting. Our study reveals a positive correlation between increased plasma NT and MMP-9 activity in both of patient’s serum and gastric cancer cell lines. A dose-dependent elevation of MMP-9 activity was observed by NT treatment in gastric cancer cells (MKN-1 and MKN-45) compared to untreated gastric cancer and normal epithelial cell (HFE-145). Moreover, NT-mediated migration and invasion were observed in gastric cancer cells unlike in normal cell. The signaling mechanism of NT in gastric cancer cells was confirmed in protein kinase C (PKC), extracellular-signal regulated kinase (ERK), and phosphatidylinositol 3-kinase (PI3K) pathway. In addition, pretreatment of gastric cancer cells with NTR1 inhibitor SR48692 was shown to significantly inhibit the NT-mediated MMP-9 activity, cell invasion, and migration. Our finding illustrated NTR1 could be a possible therapeutic target for gastric cancer.


Neurotensin NTR1 ELISA MMP-9 Invasion ERK 



This study was supported by the Creative Fusion Research Program through the Creative Allied Project funded by Korea Research Council of Science and Technology (CAP-12-1-KIST) and Korea Institute of Science and Technology (KIST) Institutional Program (project no. 2E25360).

Conflicts of interest


Supplementary material

13277_2015_3282_MOESM1_ESM.pptx (399 kb)
Supplementary Fig. 1 (PPTX 399 kb)


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Hafeza Akter
    • 1
    • 3
  • Min Park
    • 1
  • Oh-Seung Kwon
    • 2
    • 3
  • Eun Joo Song
    • 1
    • 3
  • Won-Sang Park
    • 4
  • Min-Jung Kang
    • 1
    • 3
  1. 1.Molecular Recognition Research CenterKorea Institute of Science and TechnologySeoulSouth Korea
  2. 2.Doping Control CenterKorea Institute of Science and TechnologySeoulSouth Korea
  3. 3.Department of Biological ChemistryKorea University of Science and TechnologyDaejeonSouth Korea
  4. 4.Department of Pathology, College of MedicineThe Catholic University of KoreaSeoulSouth Korea

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