Abstract
BackgroundAs a member of the ERM (ezrin-radixin-moesin) protein family, EZR has been recognized as a regulator of adhesion signal pathways by researchers. Moreover, EZR was thought to play irreplaceable roles in invasion and metastasis of versatile cancers. In this study, we managed to undermine the effect of EZR on proliferation and metastasis in pancreatic cancer (PC).MethodsTo analyze the impact of EZR expression on overall survival and free diseases survival of PC patients, we screened abnormally expressed EZR in PC using the Gene Expression Omnibus database (GEO database) and The Cancer Genome Atlas (TCGA) database. Following, Gene Ontology (GO)-based functional analysis and Gene set enrichment analysis (GSEA) was performed to predicate the possible biological processes in which EZR were involved. The clinicopathological characteristics and prognosis of PC patients were analyzed according to clinical data. Further, immunohistochemistry, western blotting and real time PCR analysis were conducted to analyze the expression level of EZR in PC and paired paracancerous tissues. The effect of EZR on proliferation of PC cell lines were detected by Cell Counting Kit-8 assay, and meanwhile, Transwell assay was performed to detect the effect of EZR on invasion and migration of PC cell.ResultEZR exhibited higher expression level in pancreatic cancer tissues and cell than paracancerous tissues and cell, and its expression level was positively correlated with poor overall survival and diseases-free survival in PC patients. CCK8 assay indicated that EZR facilitated the proliferation of PC cells, meanwhile, Transwell assay showed that EZR promoted the migration and invasion of PC cells. The GO analysis predicated that EZR was involved in biological processes including cell adhesion, ameboidal-type cell migration, cell junction assembly. Through GSEA analysis, pancreatic cancer pathway, and the adhesion junction pathway were screened as the mostly enriched pathways in EZR-regulated pathological process. The inhibition of EZR suppressed proliferation and migration of PC cells. Western blot experiment revealed a positive correlation between EZR and FAK, the proliferation invasion and migration ability of PC cells were significantly decreased after knockdown of EZR.ConclusionOur finding revealed EZR accelerated the progression of PC via FAK/AKT signaling pathway.
Highlights
Pancreatic cancer (PC) is generally acknowledged as one of the most malignant cancer which is difficult to diagnose and cure [1]
Our finding revealed EZR accelerated the progression of PC via FAK/AKT signaling pathway
Bioinformatics analysis of gene expression profiles: EZR is significantly up‐regulated in PC The GEO and The Cancer Genome Atlas (TCGA) databases were utilized to measure the expression of different genes in PC and normal pancreatic tissues, the differentially expressed genes were shown in Fig. 1A–C, Venn diagram of the differentially expressed genes in the three microarray datasets was shown in Fig. 1D, we obtained three target genes S100P, EZR and TFF1, Kaplan–Meier survival analysis demonstrated that PC patients with high expression of EZR was positively correlated with diagnosis in overall survival rate (OS) and disease free survival (DFS) according to GEPIA database (Fig. 1E, F)
Summary
Pancreatic cancer (PC) is generally acknowledged as one of the most malignant cancer which is difficult to diagnose and cure [1]. Surgery is recognized as the main treatment for pancreatic cancer, while 70–80% of patients have no surgical opportunity when they were diagnosed, the recurrence rate of PC patients undergone resection is extremely high due to metastasis of tumor [4, 5]. Though the growth of a certain number of PC patients’ survival has witnessed the potential of targeted biological therapy to effectively improve prognosis, it still exists huge obstacles for the prognosis of PC since early local tumor invasion, metastasis and multi-drug resistance. They are ranking the primary cause of low survival rate in PC [6, 7]. We managed to undermine the effect of EZR on proliferation and metastasis in pancreatic cancer (PC)
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