title: Dopamine D2 receptor suppresses gastric cancer cell invasion and migration via inhibition of EGFR/AKT/MMP-13 pathway.
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.
authors.affiliation: Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Huang
authors.affiliation: Gastrointestinal Surgery Center, The first Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China.
authors.forename: Kaiming
authors.initials: K
authors.lastname: Wu
authors.affiliation: Department of Thoracic Surgery, The first Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, China.
authors.forename: Yanlei
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, China.
authors.forename: Chuangyu
authors.initials: C
authors.lastname: Cao
authors.affiliation: Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, China. Electronic address: yongqnie@163.com.
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Nie
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D063646:Carcinogenesis / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004298:Dopamine / Q000627:therapeutic use*; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D017448:Receptors, Dopamine D2; D004815:Epidermal Growth Factor; C512478:EGFR protein, human; D066246:ErbB Receptors; D051058:Oncogene Protein v-akt; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D004298:Dopamine
keywords: AKT; Dopamine D2 receptor; EGFR; Gastric cancer; Invasion; MMP-13