Dopamine D2 receptor suppresses gastric cancer cell invasion and migration via inhibition of EGFR/AKT/MMP-13 pathway |
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| Affiliation: | 1. Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People''s Hospital, Guangzhou Medical University, Guangzhou 510180, China;2. Gastrointestinal Surgery Center, The first Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China;3. Department of Thoracic Surgery, The first Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China;1. Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran;2. Cancer Molecular Research Center, Ghaem Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran;1. Institute of Infection, Immunity and Inflammation, University of Glasgow, G12 8TA, United Kingdom;2. Institute of Cellular Medicine, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK;3. Institute of Transplantation, Freeman Hospital, Newcastle upon Tyne NE7 7DN, UK;4. Paediatric Respiratory Medicine, Great North Children''s Hospital, Queen Victoria Road, Newcastle upon Tyne NE1 4LP, UK |
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| Abstract: | Dopamine (DA), an important neurotransmitter, has been reported to play a negative role in tumor progression. DA acts its role via dopamine receptors (DRs), which can be divided into five receptor subtypes (D1R-D5R). Among these receptor subtypes, D2R has been found to inhibit IGF-I-induced gastric cancer cell growth. However, the functions of D2R in gastric cancer cell invasion remain elusive. Here, we found that D2R expression was decreased in gastric cancer cells. DA treatment dose-dependently inhibited EGF-mediated gastric cancer cell invasion and migration via D2R. Furthermore, D2R decreased EGF-mediated MMP-13 production, and attenuated EGFR and AKT activation. Together with the results that EGF promoted gastric cancer cell invasion and migration via EGFR/AKT pathway, these data indicate that DA treatment, acting via D2R, suppresses gastric cancer cell invasion and migration via inhibition of EGFR/AKT/MMP-13 pathway. Thus, our findings suggest that use of D2R agonist may have a potential therapeutic effect on gastric cancer. |
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