RRC ID 45173
Author Saito K, Iizuka Y, Ohta S, Takahashi S, Nakamura K, Saya H, Yoshida K, Kawakami Y, Toda M.
Title Functional analysis of a novel glioma antigen, EFTUD1.
Journal Neuro Oncol
Abstract BACKGROUND:A cDNA library made from 2 glioma cell lines, U87MG and T98G, was screened by serological identification of antigens by recombinant cDNA expression (SEREX) using serum from a glioblastoma patient. Elongation factor Tu GTP binding domain containing protein 1 (EFTUD1), which is required for ribosome biogenesis, was identified. A cancer microarray database showed overexpression of EFTUD1 in gliomas, suggesting that EFTUD1 is a candidate molecular target for gliomas.
METHODS:EFTUD1 expression in glioma cell lines and glioma tissue was assessed by Western blot, quantitative PCR, and immunohistochemistry. The effect on ribosome biogenesis, cell growth, cell cycle, and induction of apoptosis and autophagy in glioma cells during the downregulation of EFTUD1 was investigated. To reveal the role of autophagy, the autophagy-blocker, chloroquine (CQ), was used in glioma cells downregulating EFTUD1. The effect of combining CQ with EFTUD1 inhibition in glioma cells was analyzed.
RESULTS:EFTUD1 expression in glioma cell lines and tissue was higher than in normal brain tissue. Downregulating EFTUD1 induced G1 cell-cycle arrest and apoptosis, leading to reduced glioma cell proliferation. The mechanism underlying this antitumor effect was impaired ribosome biogenesis via EFTUD1 inhibition. Additionally, protective autophagy was induced by glioma cells as an adaptive response to EFTUD1 inhibition. The antitumor effect induced by the combined treatment was significantly higher than that of either EFTUD1 inhibition or CQ alone.
CONCLUSION:These results suggest that EFTUD1 represents a novel therapeutic target and that the combination of EFTUD1 inhibition with autophagy blockade may be effective in the treatment of gliomas.
Volume 16(12)
Pages 1618-29
Published 2014-12-1
DOI 10.1093/neuonc/nou132
PII nou132
PMID 25015090
PMC PMC4232085
MeSH Antigens, Neoplasm / immunology Antigens, Neoplasm / metabolism Antigens, Neoplasm / physiology Apoptosis Autophagy Brain Neoplasms / immunology* Brain Neoplasms / metabolism* Cell Cycle Cell Line, Tumor Down-Regulation Eukaryotic Initiation Factors / metabolism Gene Library Glioma / immunology* Glioma / metabolism* Humans Peptide Elongation Factors / immunology Peptide Elongation Factors / metabolism Peptide Elongation Factors / physiology* Ribonucleoprotein, U5 Small Nuclear / immunology Ribonucleoprotein, U5 Small Nuclear / metabolism Ribonucleoprotein, U5 Small Nuclear / physiology* Ribosomes / metabolism
IF 10.247
Times Cited 5
Human and Animal Cells U251(RCB0461)