Influence of eukaryotic translation initiation factor 6 on non–small cell lung cancer development and progression

Abstract

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. Dysregulation of protein synthesis plays a major role in carcinogenesis, a process regulated at multiple levels, including translation of mRNA into proteins. Ribosome assembly requires correct association of ribosome subunits, which is ensured by eukaryotic translation initiation factors (eIFs). eIFs have become targets in cancer therapy studies, and promising data on eIF6 in various cancer entities have been reported. Therefore, we hypothesised that eIF6 represents a crossroad for pulmonary carcinogenesis. High levels of eIF6 are associated with shorter patient overall survival in adenocarcinoma (ADC), but not in squamous cell carcinoma (SQC) of the lung. We demonstrate significantly higher protein expression of eIF6 in ADC and SQC than in healthy lung tissue based on immunohistochemical data from tissue microarrays (TMAs) and on fresh frozen lung tissue. Depletion of eIF6 in ADC and SQC lung cancer cell lines inhibited cell proliferation and induced apoptosis. Knockdown of eIF6 led to pre-rRNA processing and ribosomal 60S maturation defects. Our data indicate that eIF6 is upregulated in NSCLC, suggesting an important contribution of eIF6 to the development and progression of NSCLC and a potential for new treatment strategies against NSCLC.

Discovery and Preliminary Characterization of Translational Modulators that Impair the Binding of eIF6 to 60S Ribosomal Subunits

“…eIF6 activity is heavily affected in tumor cells and its modulation has a potential value in both cancer and genetically inherited diseases. A high expression of eIF6 correlates with human cancer malignancy and progression [20][21][22][23]. Studies in mice have unequivocally shown that eIF6 levels control cancer progression and mortality.…”

RPV‐modified epirubicin and dioscin co‐delivery liposomes suppress non‐small cell lung cancer growth by limiting nutrition supply

“…Lung cancer is one of the most common malignancies and a leading cause of cancer‐related death worldwide . Among all lung cancers, approximately 85% are non‐small cell lung cancer (NSCLC), for which morbidity is significantly higher than for small cell lung cancer .…”

Leveraging methylation to identify the potential causal genes associated with survival in lung adenocarcinoma and lung squamous cell carcinoma

“…Previous studies have demonstrated that differentially expressed genes (DEGs) serve an important role in the progression of both LUAD and LUSC (9)(10)(11). Gantenbein et al (12) have identified that upregulation of eukaryotic translation initiation factor 6 in NSCLC is associated with poor overall survival in LUAD, but not in LUSC. Qu et al (13) have demonstrated that interleukin-6 prevents the initiation, but enhances the progression of LC in a mouse model.…”