High intratumoral expression of eIF4A1 promotes epithelial-to-mesenchymal transition and predicts unfavorable prognosis in gastric cancer

Abstract

Gastric cancer is an important health problem, being the fifth most common cancer and the third leading cause of cancer-related death worldwide. Aberrant protein translation contributes to the oncogenesis and development of cancers, and upregulation of translation initiation factor eIF4A1 has been observed in several kinds of malignancies. However, the role of eIF4A1 in gastric cancer progression remains unclear. In this study, we found that the expression of eIF4A1, a component of translation initiation complex, was increased in gastric cancer. High expression of eIF4A1 was positively associated with poor tumor differentiation, late T stage, lymph node metastasis, advanced TNM stage, and poor prognosis in patients with gastric cancer. Overexpression of eIF4A1 promoted the migration and invasion of gastric cancer cells in vitro and enhanced tumor metastasis in nude mice model. Mechanism studies revealed that eIF4A1 induced epithelial-to-mesenchymal transition (EMT) of gastric cancer cells through driving the translation of SNAI1 mRNA. Together, these findings indicate that eIF4A1 promotes EMT and metastasis of gastric cancer and suggest that eIF4A1 is a potential target for the adjuvant therapy for gastric cancer patients.

Expression and Functional Roles of Eukaryotic Initiation Factor 4A Family Proteins in Human Cancers

“…Wei et al demonstrated that the expression levels of eIF4A1 protein were upregulated in 74 clinical GC samples (Wei et al, 2019), similar to the results obtained by other research teams (Li et al, 2020a). Additionally, the overexpression of eIF4A1 has been positively associated with advanced tumor-node-metastasis (TNM) stage, poor tumor differentiation, and a poor prognosis in patients with GC (Gao et al, 2020).…”

“…Similarly, immunohistochemical staining of the eIF4A1 protein in patients with GC showed that eIF4A1 protein levels are generally increased in tumor tissues (Gao et al, 2020). Wei et al demonstrated that the expression levels of eIF4A1 protein were upregulated in 74 clinical GC samples (Wei et al, 2019), similar to the results obtained by other research teams (Li et al, 2020a).…”

“…The eIF4F translation initiation complex controls the translation initiation rates of many pro-oncogenic mRNAs and serves as a critical node under the regulation of the PI3K/Akt/mTOR signaling pathway (Lin et al, 2008), the mitogen-activated protein kinase signal transduction pathway, and the caspase-dependent apoptotic pathway (Blagden and Willis, 2011). As an important component of eIF4F, eIF4A1 plays a vital role in malignant transformation and progression, and recent evidence has shown that eIF4A1 is dysregulated in gastric cancer (GC) (Gao et al, 2020), colorectal cancer (Li W. et al, 2017), cervical cancer (Liang et al, 2014), hepatocellular carcinoma (Zhang et al, 2020), ovarian cancer (Zhang et al, 2018), and other cancers.…”

“…Gao et al examined the mRNA expression levels of eIF4A1 in GC by employing the Gene Expression Omnibus (GEO) and showed that eIF4A1 mRNA is significantly upregulated in GC tissues compared to adjacent normal tissues (Gao et al, 2020).…”

Development and Validation of Nine-RNA Binding Protein Signature Predicting Overall Survival for Kidney Renal Clear Cell Carcinoma

“…Among the nine RBPs, EEF1A2, and RPL13 have been reported to be associated with tumorigenesis and progression of kidney cancer patients ( Pflueger et al, 2013 ; Wierzbicki et al, 2014 ). Eukaryotic translation initiation factor 4A1 (EIF4A1) is a component of the translation initiation complex, and a high expression level of EIF4A1 is positively associated with poor tumor differentiation, late T stage, lymph node metastasis, advanced TNM stage, and poor prognosis in patients with gastric cancer ( Gao et al, 2020 ). Overexpression of ribosomal protein L36a (RPL36A) has been reported to closely relate to cellular proliferation in hepatocellular carcinoma ( Kim et al, 2004 ).…”