PMID- 25015090
OWN - NLM
STAT- MEDLINE
DCOM- 20150706
LR  - 20211021
IS  - 1523-5866 (Electronic)
IS  - 1522-8517 (Print)
IS  - 1522-8517 (Linking)
VI  - 16
IP  - 12
DP  - 2014 Dec
TI  - Functional analysis of a novel glioma antigen, EFTUD1.
PG  - 1618-29
LID - 10.1093/neuonc/nou132 [doi]
AB  - 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.
CI  - (c) The Author(s) 2014. Published by Oxford University Press on behalf of the 
      Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: 
      journals.permissions@oup.com.
FAU - Saito, Katsuya
AU  - Saito K
AD  - 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.).
FAU - Iizuka, Yukihiko
AU  - Iizuka Y
AD  - 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.).
FAU - Ohta, Shigeki
AU  - Ohta S
AD  - 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.).
FAU - Takahashi, Satoshi
AU  - Takahashi S
AD  - 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.).
FAU - Nakamura, Kenta
AU  - Nakamura K
AD  - 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.).
FAU - Saya, Hideyuki
AU  - Saya H
AD  - 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.).
FAU - Yoshida, Kazunari
AU  - Yoshida K
AD  - 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.).
FAU - Kawakami, Yutaka
AU  - Kawakami Y
AD  - 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.).
FAU - Toda, Masahiro
AU  - Toda M
AD  - 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.).
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140711
PL  - England
TA  - Neuro Oncol
JT  - Neuro-oncology
JID - 100887420
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (EFL1 protein, human)
RN  - 0 (EIF6 protein, human)
RN  - 0 (Eukaryotic Initiation Factors)
RN  - 0 (Peptide Elongation Factors)
RN  - 0 (Ribonucleoprotein, U5 Small Nuclear)
SB  - IM
MH  - Antigens, Neoplasm/immunology/metabolism/physiology
MH  - Apoptosis
MH  - Autophagy
MH  - Brain Neoplasms/*immunology/*metabolism
MH  - Cell Cycle
MH  - Cell Line, Tumor
MH  - Down-Regulation
MH  - Eukaryotic Initiation Factors/metabolism
MH  - Gene Library
MH  - Glioma/*immunology/*metabolism
MH  - Humans
MH  - Peptide Elongation Factors/immunology/metabolism/*physiology
MH  - Ribonucleoprotein, U5 Small Nuclear/immunology/metabolism/*physiology
MH  - Ribosomes/metabolism
PMC - PMC4232085
OTO - NOTNLM
OT  - EFTUD1
OT  - SEREX
OT  - autophagy
OT  - glioma
OT  - ribosome biogenesis
EDAT- 2014/07/13 06:00
MHDA- 2015/07/07 06:00
PMCR- 2015/12/01
CRDT- 2014/07/13 06:00
PHST- 2014/07/13 06:00 [entrez]
PHST- 2014/07/13 06:00 [pubmed]
PHST- 2015/07/07 06:00 [medline]
PHST- 2015/12/01 00:00 [pmc-release]
AID - nou132 [pii]
AID - 10.1093/neuonc/nou132 [doi]
PST - ppublish
SO  - Neuro Oncol. 2014 Dec;16(12):1618-29. doi: 10.1093/neuonc/nou132. Epub 2014 Jul 
      11.