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

• Published in: Molecules and cells Vol. 41; no. 6; pp. 591 - 602
• Main Authors: Akter, Hafeza, Yoon, Jung Hwan, Yoo, Young Sook, Kang, Min-Jung
• Format: Journal Article
• Language: English
• Published: United States Korean Society for Molecular and Cellular Biology 01.06.2018; 한국분자세포생물학회
• Subjects: Cell Line, Tumor; Female; Humans; Male; Receptors, Neurotensin - genetics; Receptors, Neurotensin - metabolism; Stomach Neoplasms - genetics; Stomach Neoplasms - mortality; Stomach Neoplasms - pathology; Survival Rate; 생물학; neurotensin; gastric cancer; MMP-9; NTSR1
• ISSN: 1016-8478; 0219-1032
• DOI: 10.14348/molcells.2018.0025

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.