Sumoylation of eukaryotic elongation factor 2 is vital for protein stability and anti-apoptotic activity in lung adenocarcinoma cells

Abstract

By screening mouse monoclonal antibody libraries for Kelch repeats, we serendipitously identified monoclonal antibodies to eukaryotic elongation factor 2 (eEF2). Interestingly, eEF2 was highly expressed in lung adenocarcinoma (LADC), but not in the neighboring non-tumor lung tissue. Normally, eEF2 is involved in the peptidyl-tRNA translocation during protein synthesis. Overexpression of eEF2 would implicate an association with disease progression of LADC. In the present study, we investigated the prognostic significance of eEF2 in patients with LADC. Expression of eEF2 was detected by immunoblotting, immunohistochemistry and confocal immunofluorescence microscopy. Our results show that patients with high eEF2 expression had a significantly higher incidence of early tumor recurrence (67.8%vs 18.2%, P=0.016), and a significantly worse prognosis (P<0.001). In an in vitro study, silencing of eEF2 expression increased mitochondrial elongation, cellular autophagy and cisplatin sensitivity. Moreover, eEF2 was sumoylated in LADC cells, and eEF2 sumoylation correlated with drug resistance. These results suggest that eEF2 is an anti-apoptotic marker in LADC. However, biological function and involvement of eEF2 in the disease progression of LADC require further studies. © 2011 Japanese Cancer Association.