| Moesin has been demonstrated to be associated with the recurrence and metastasis of many cancers.However,data are still limited in liver cancer.In the previous study of our research group,i TRAQ quantitative proteomics was used to analyze the differential proteins in hepatocellular carcinoma(HCC)cell lines with different invasion and migration potentials,and the significantly differential protein including Moesin.Based on the previous studies,this paper aimed to investigate the clinical significance and biological function of Moesin in HCC.First of all,HCC tissues(both tumor and non-tumor)were collected from 91 patients and the relative expression of Moesin were evaluated by immunohistochemical staining.Then,Transwell and wound-healing experiments were used to study the effects of Moesin on the migration and invasion of HCC cells by overexpression and knockdown of Moesin in HCC cell lines.Western blot(WB)and Laser scanning confocal microscope(CLSM)were used to detect the protein expression and localization of key factors related to metastasis.Simultaneously,HCC pulmonary metastasis mice model was also constructed to further verify the effects of Moesin on the metastasis of HCC cells in vivo.Firstly,we found that the expression level of Moesin in HCC tissues was significantly higher than that in adjacent tissues(p < 0.0001).Moesin expression was significantly correlated with tumor size(p = 0.009),tumor differentiation(p = 0.004),satellite lesion(p = 0.008),microvascular invasion(p = 0.0001)and recurrence(p = 0.008).Furthermore,KaplanMeier(K-M)curve analysis revaled that recurrence-free survival was shorter in patients with high Moesin expression in HCC patients(p < 0.0001).Likewise,Cox regression analysis proved that Moesin is an independent factor for evaluating the postoperative recurrence risk of HCC patients.Secondly,Moesin was overexpressed and knocked down in SMMC-7721 and SK-Hep-1 cells,respectively.Transwell and wound-healing experiments showed that overexpression of Moesin could significantly promote the migration and invasion of HCC cells,while,the opposite result in the knockdown of Moesin.In addtion,Moesin significantly advanced the tumor metastasis in mice model of HCC pulmonary metastasis.The mechanism study found that Moesin could significantly increase the expression level of F-actin and promote the formation of invadopodia.Moreover,overexpression of Moesin increased the expressions of ?-catenin and downstream migration-promoting gene MMP9 by WB.Overexpression of Moesin could induce nuclear translocation of ?-catenin by CLSM,that is to increase the activity of ?-catenin transcription factor.The expressions of Moesin and ?-catenin were significant-positively correlated by statistical analysis of TCGA dataset.And those results further support our conclusions that Moesin may promote the migration and invasion of HCC cells through advancing the formation of invadopodia and activating the ?-catenin/ MMP9 signal axis.In conclusion,significantly up-regulated Moesin is associated with poor prognosis and is a potential marker for assessing the risk of recurrence in patients with liver cancer.Moesin promotes the invasion and metastasis of HCC cells by increasing invadopodia and activating ?-catenin/MMP9 signaling axis. |
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