Functional analysis of a novel glioma antigen, EFTUD1

Katsuya Saito, Yukihiko Iizuka, Shigeki Ohta, Satoshi Takahashi, Kenta Nakamura, Hideyuki Saya, Kazunari Yoshida, Yutaka Kawakami, Masahiro Toda

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1618-1629
Number of pages12
JournalNeuro-oncology
Volume16
Issue number12
DOIs
Publication statusPublished - 2014

Keywords

  • Autophagy
  • EFTUD1
  • Glioma
  • Ribosome biogenesis
  • SEREX

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

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