The Role Of ELMO2 In The Invasion And Metastasis Of Gastric Cancer

Background:Gastric cancer(GC)is the fifth most common cancer and the third leading cause of death from malignant tumor worldwide.GC is often confirmed at advanced stage due to the absence of specific symptoms and early diagnostic markers,however the cure of late stage is unattainable.Besides,high mortality of GC is closely related with the high rate of recurrence and metastasis after surgical radical resection.Recently,studies revealed that the engulfment and cell motility(ELMO)proteins family plays a pivotal role in the metastasis and invasion of cancer cell movement.Therefore,the mechanism underlining the metastasis and recurrence of GC needs to further exploration,meanwhile,it's urgent to find a new biomarker and potential therapeutic target for early detection,prognosis prediction and targeted therapy of GC.Objective:This reaserch was designed to detect the expression level of ELMO2 in tumor tissues and to analyze the relationship between the clinicopathologic parameters with the ELMO2 level of GC patients.Then,we blocked the elmo2 gene via RNAi in vitro,observed the changes of cell proliferation,invasion,metastasis,cell cycle and F-actin polymerization.Methods:1.41 tumor tissue and 41 adjacent normal tissue specimens form GC patients were collected for studying.The RT-qPCR and Western blot were taken to detect the ELMO2 mRNA and protein level of these GC tissue samples.The positive expression and location of ELMO2 in tissues was measured by IHC.Analysis of the significance between the expression level of ELMO2 and the clinical characters of these GC patients.2.In cell experiments,RNAi was used to elmo2 gene knockout in SGC7901 and BGC823 of gastric cancer cell lines.Transwell assay,MTS assays,flow cytometry technique and fluorescent microscope staining were taken to verify the effect of ELMO2 down-regulation on the changes of biological behavior,such as migration,invasion,cell proliferation,cell cycle,and cytoskeletal F-actin polymerization.Results:1.The results of RT-qPCR,Western-blot and IHC showed that the mRNA and protein expression levels of ELMO2 in GC tissues were significantly higher than those in adjacent tissues,and the expression level of ELMO2 in GC tissues with lymph node metastasis was significantly higher than that in tissues without lymph node metastasis.2.Analysis of clinicopathologic characters from forty-one GC patients revealed that there was a significant difference in the expression of ELMO2 with GC tumor size,depth of invasion,lymph node metastasis,distant metastasis and TNM stage,but there was no significance with the gender and age of these patients.3.The down-regulated expression of ELMO2 in gastric cancer cell lines SGC7901 and BGC823 cells in vitro exhibit inhibition of cell migration,invasion and proliferation.Besides,silencing elmo2 resulted in the failure of cytoskeletal F-actin polymerization and the arrest of cell cycle in G1 phase.Conclusion:1.The ELMO2 protein was over-expressed in GC tissues,and the expression level of ELMO2 was correlated with tumor size,invasive depth,lymph node metastasis,distant metastasis,and TNM stage.2.The ELMO2 could stimulate the proliferation,invasion,migration of SGC7901 and BGC823 cell lines,and plays a crucial role in the remodeling of cytoskeleton Factin.