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Validation of Neurotensin Receptor 1 as a Therapeutic Target for Gastric Cancer

  • Akter, Hafeza (Molecular Recognition Research Center, Korea Institute of Science and Technology) ;
  • Yoon, Jung Hwan (Department of Pathology, College of Medicine, The Catholic University of Korea) ;
  • Yoo, Young Sook (Molecular Recognition Research Center, Korea Institute of Science and Technology) ;
  • Kang, Min-Jung (Molecular Recognition Research Center, Korea Institute of Science and Technology)
  • Received : 2018.01.08
  • Accepted : 2018.03.20
  • Published : 2018.06.30

Abstract

Gastric cancer is the fifth most common type of malignancy worldwide, and the survival rate of patients with advanced-stage gastric cancer is low, even after receiving chemotherapy. Here, we validated neurotensin receptor 1 (NTSR1) as a potential therapeutic target in gastric cancer. We compared NTSR1 expression levels in sixty different gastric cancer-tissue samples and cells, as well as in other cancer cells (lung, breast, pancreatic, and colon), by assessing NTSR1 expression via semi-quantitative real-time reverse transcription polymerase chain reaction, immunocytochemistry and western blot. Following neurotensin (NT) treatment, we analyzed the expression and activity of matrix metalloproteinase-9 (MMP-9) and further determined the effects on cell migration and invasion via wound-healing and transwell assays. Our results revealed that NTSR1 mRNA levels were higher in gastric cancer tissues than non-cancerous tissues. Both of NTSR1 mRNA levels and expression were higher in gastric cancer cell lines relative to levels observed in other cancer-cell lines. Moreover, NT treatment induced MMP-9 expression and activity in all cancer cell lines, which was significantly decreased following treatment with the NTSR1 antagonist SR48692 or small-interfering RNA targeting NTSR1. Furthermore, NT-mediated metastases was confirmed by observing epithelial-mesenchymal transition markers SNAIL and E-cadherin in gastric cancer cells. NT-mediated invasion and migration of gastric cancer cells were reduced by NTSR1 depletion through the Erk signaling. These findings strongly suggested that NTR1 constitutes a potential therapeutic target for the inhibition of gastric cancer invasion and metastasis.

Acknowledgement

Supported by : Korea Research Council of Science and Technology, National Research Foundation of Korea (NRF), Korea Institute of Science and Technology (KIST)

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