The Role Of G-protein-coupled Receptor 120 In Human Esophageal Cancer And Its Related Mechanisms

Esophageal cancer is considered a serious malignancy with respect to prognosis and mortality rate.Accounting for more than 40,000 deaths worldwide in 2005.Esophageal carcinoma is the eighth most common cancer,and the sixth most common cause of cancer related deaths worldwide with developing nations making up more than 80% of total cases and deaths.the prevalence of esophageal cancer is expected to increase by 140% by 2025.Despite many advances in diagnosis and treatment,the 5-year survival rate for all patients diagnosed with esophageal cancer ranges from 15% to 20%.Dysregulated G-protein-coupled receptor(GPCR)expression and dysregulation of GPCR signaling has been recognized as a hallmark of cancer.Recently,several GPCRs identified as free fatty acid receptors have emerged as key players in various physiological homeostasis mechanisms.GPR120 is one of the receptors.In present study,we will discuss the role of GPR120 in the development of esophageal cancer.We will explore the relationship between GPR120 and esophageal cancer,discuss the function and mechanisms of GPR120 in esophageal cancer to elucidate the role of GPR120 in the development of esophageal cancer.Part ? The expression of G protein couple receptor 120 in patients with esophageal cancer and its correlation with clinical parametersObjective: The aim of this study was to investigate the expression of GPR120 in patients with esophageal cancer and explore its relationship with clinical parameters.Methods: The esophageal cancer tissues and adjacent control tissues were collected from the patients who confirmed with esophageal cancer.Immunohistochemical analysis was performed to examine the expression of GPR120.All the included patients were then classified into high and low GPR120 expression group according to the immunohistochemical results.The demographic data of the patients,including age,gender,tumor size,tumor position,tumor grade,invasion depth and lymph node metastasis.Chisquare test was employed to examine the correlations between GPR120 expression level and clinical parameters.Results: According to the immunohistochemical results,the positive staining of GPR120 was mainly located in the cell membrane and cytoplasm,while negative expression of GPR120 was found in the adjacent normal tissues.The statistical analysis results showed that GPR120 expression was not significantly correlated with age,gender,histology classification,tumor size and tumor position,while significant correlations were found between GPR120 expression and histology classification,tumor grade,invasion depth and lymph node metastasis.Conclusions: High expression of GPR120 was found in patients with esophageal cancer,which was correlated with histology classification and metastasis property of the tumor.Part ? The expression of GPR120 in esophageal cancer cell line and its effect on biological behavior change of the esophageal cancer cellObjective: The aim of this study was to investigate the expression of GPR120 in esophageal cancer cell line and explore its effect on the biological behavior change of esophageal cancer cell.Methods: We collected 3 esophageal cancer cell lines(Eca-109,TE-1 and KYS450)and immnoblot was employed to examine the expression of GPR120 in these cell lines.The cell line with highest expression of GPR120 was selected and performed with gene knockdown with lentivirus infection.After that,the cell proliferation,clone formation,cell migration and invasion was performed to explore the effect of GPR120 in esophageal cancer cell.Moreover,we also observe the effect of GPR120 on the tumor formation by using xenotransplantion nude mice model.Results: The highest expression of GPR120 was found in Eca-109 cells.After identification of the GPR120 knockdown by realtime PCR,immunoblot,flow cytometry,we successfully performed the expression knockdown of GPR120 in esophageal cancer cell line Eca-109.The in vitro assay results showed that GPR120 knockdwon could significantly downregulate the cell proliferation,clone formation,cell migration and invasion.The results from the Eca-109 xenotransplantion nude mice model showed that GPR120 knockdown could significantly downregulate the tumor formation ability in nude mice.Conclusions: GPR120 could positively regulates the cell proliferation,clone formation,migration and invasion in vitro and in vivo.Part ? The regulation mechanisms of GPR120 in esophageal cancer cell lineObjective: The aim of this study was to investigate the regulation mechanisms of GPR120 in esophageal cancer cell line.Methods: We used the above established GPR120 knockdown Eca-109 esophageal cancer cell and control lines to explore the molecular mechanism from the view of epthelial mesenchymal transition(EMT),PI3 K pathway,NF-?B pathway and vascular and inflammatory cytokines.Results: We found that compared to the control cells,GPR120 knockdown in cancer cell line could upgeglate the expression of E-cadherin and downregulate the expression of N-cadherin and vimentin at 24,48 and 72 h.Moreover,we found that GPR120 knockdown in cancer cell line could downregulate the Akt phosphorylation and I?B phosphorylation at0,5,15,30,60 min.In addition,GPR120 knockdown in cancer cell line could significantly downregulate the m RNA of VEGF,IL-8 and Cox-2.At the same time,GPR120 knockdown in cancer cell line could significantly downregulate protein level of VEGF,IL-8 and PGE2 in cell culture supernant.Conclusions: GPR120 could regulates the biological behavior of esophageal cancer cell by affecting EMT,PI3 K pathway,NF-?B pathway and vascular and inflammatory cytokines.