title: Functional analysis of a novel glioma antigen, EFTUD1.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan (K.S., S.T., K.Y., M.T.); Neuro-immunology Research Group, Keio University School of Medicine, Tokyo, Japan (Y.I., S.O., M.T.); Department of Physiology, Keio University School of Medicine, Tokyo, Japan (S.O.); Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan (K.N., Y.K.); Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan (H.S.).
authors.forename: Katsuya
authors.initials: K
authors.lastname: Saito
authors.affiliation: Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan (K.S., S.T., K.Y., M.T.); Neuro-immunology Research Group, Keio University School of Medicine, Tokyo, Japan (Y.I., S.O., M.T.); Department of Physiology, Keio University School of Medicine, Tokyo, Japan (S.O.); Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan (K.N., Y.K.); Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan (H.S.).
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Iizuka
authors.affiliation: Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan (K.S., S.T., K.Y., M.T.); Neuro-immunology Research Group, Keio University School of Medicine, Tokyo, Japan (Y.I., S.O., M.T.); Department of Physiology, Keio University School of Medicine, Tokyo, Japan (S.O.); Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan (K.N., Y.K.); Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan (H.S.).
authors.forename: Shigeki
authors.initials: S
authors.lastname: Ohta
authors.affiliation: Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan (K.S., S.T., K.Y., M.T.); Neuro-immunology Research Group, Keio University School of Medicine, Tokyo, Japan (Y.I., S.O., M.T.); Department of Physiology, Keio University School of Medicine, Tokyo, Japan (S.O.); Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan (K.N., Y.K.); Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan (H.S.).
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan (K.S., S.T., K.Y., M.T.); Neuro-immunology Research Group, Keio University School of Medicine, Tokyo, Japan (Y.I., S.O., M.T.); Department of Physiology, Keio University School of Medicine, Tokyo, Japan (S.O.); Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan (K.N., Y.K.); Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan (H.S.).
authors.forename: Kenta
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan (K.S., S.T., K.Y., M.T.); Neuro-immunology Research Group, Keio University School of Medicine, Tokyo, Japan (Y.I., S.O., M.T.); Department of Physiology, Keio University School of Medicine, Tokyo, Japan (S.O.); Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan (K.N., Y.K.); Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan (H.S.).
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Saya
authors.affiliation: Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan (K.S., S.T., K.Y., M.T.); Neuro-immunology Research Group, Keio University School of Medicine, Tokyo, Japan (Y.I., S.O., M.T.); Department of Physiology, Keio University School of Medicine, Tokyo, Japan (S.O.); Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan (K.N., Y.K.); Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan (H.S.).
authors.forename: Kazunari
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan (K.S., S.T., K.Y., M.T.); Neuro-immunology Research Group, Keio University School of Medicine, Tokyo, Japan (Y.I., S.O., M.T.); Department of Physiology, Keio University School of Medicine, Tokyo, Japan (S.O.); Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan (K.N., Y.K.); Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan (H.S.).
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kawakami
authors.affiliation: Department of Neurosurgery, Keio University School of Medicine, Tokyo, Japan (K.S., S.T., K.Y., M.T.); Neuro-immunology Research Group, Keio University School of Medicine, Tokyo, Japan (Y.I., S.O., M.T.); Department of Physiology, Keio University School of Medicine, Tokyo, Japan (S.O.); Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan (K.N., Y.K.); Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan (H.S.).
authors.forename: Masahiro
authors.initials: M
authors.lastname: Toda
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D017209:Apoptosis; D001343:Autophagy; D001932:Brain Neoplasms / Q000276:immunology* / Q000378:metabolism*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D015536:Down-Regulation; D039642:Eukaryotic Initiation Factors / Q000378:metabolism; D015723:Gene Library; D005910:Glioma / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D010445:Peptide Elongation Factors / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D017415:Ribonucleoprotein, U5 Small Nuclear / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D012270:Ribosomes / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; C000599132:EFL1 protein, human; C109284:EIF6 protein, human; D039642:Eukaryotic Initiation Factors; D010445:Peptide Elongation Factors; D017415:Ribonucleoprotein, U5 Small Nuclear
keywords: EFTUD1; SEREX; autophagy; glioma; ribosome biogenesis