PMID- 38102738
OWN - NLM
STAT- MEDLINE
DCOM- 20240304
LR  - 20240304
IS  - 1756-2651 (Electronic)
IS  - 0021-924X (Linking)
VI  - 175
IP  - 3
DP  - 2024 Mar 4
TI  - Merlin/NF2 regulates SLC7A11/xCT expression and cell viability under glucose 
      deprivation at high cell density in glioblastoma cells.
PG  - 313-322
LID - 10.1093/jb/mvad105 [doi]
AB  - The cystine/glutamate transporter SLC7A11/xCT is highly expressed in many cancer 
      cells and plays an important role in antioxidant activity by supplying cysteine 
      for glutathione synthesis. Under glucose-depleted conditions, however, 
      SLC7A11-mediated cystine uptake causes oxidative stress and cell death called 
      disulfidptosis, a new form of cell death. We previously reported that high cell 
      density (HD) promotes lysosomal degradation of SLC7A11 in glioblastoma cells, 
      allowing them to survive under glucose-depleted conditions. In this study, we 
      found that the neurofibromatosis type 2 gene, Merlin/NF2 is a key regulator of 
      SLC7A11 in glioblastoma cells at HD. Deletion of Merlin increased SLC7A11 protein 
      level and cystine uptake at HD, leading to promotion of cell death under glucose 
      deprivation. Furthermore, HD significantly decreased SLC7A11 mRNA level, which 
      was restored by Merlin deletion. This study suggests that Merlin suppresses 
      glucose deprivation-induced cell death by downregulating SLC7A11 expression in 
      glioblastoma cells at HD.
CI  - (c) The Author(s) 2023. Published by Oxford University Press on behalf of the 
      Japanese Biochemical Society. All rights reserved.
FAU - Yamaguchi, Itsuki
AU  - Yamaguchi I
AD  - Laboratory of Molecular Neurobiology, Graduate School of Biostudies, Kyoto 
      University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
AD  - Department of Biological Chemistry, Graduate School of Science, Osaka 
      Metropolitan University, Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.
FAU - Katoh, Hironori
AU  - Katoh H
AUID- ORCID: 0000-0002-8191-8117
AD  - Department of Biological Chemistry, Graduate School of Science, Osaka 
      Metropolitan University, Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.
LA  - eng
GR  - 21K06065 and 22J15887/Grants-in-aid for Scientific Research from the Japan 
      Society for the Promotion of Science/
PT  - Journal Article
PL  - England
TA  - J Biochem
JT  - Journal of biochemistry
JID - 0376600
RN  - 0 (Neurofibromin 2)
RN  - 48TCX9A1VT (Cystine)
RN  - IY9XDZ35W2 (Glucose)
RN  - 0 (SLC7A11 protein, human)
RN  - 0 (Amino Acid Transport System y+)
SB  - IM
MH  - Humans
MH  - *Neurofibromin 2
MH  - Cell Survival
MH  - *Glioblastoma
MH  - Cystine
MH  - Glucose
MH  - Cell Count
MH  - Amino Acid Transport System y+/genetics
OTO - NOTNLM
OT  - amino acid transport
OT  - cell death
OT  - cell density
OT  - glioblastoma
OT  - transcriptional regulation
EDAT- 2023/12/16 11:43
MHDA- 2024/03/04 06:43
CRDT- 2023/12/16 00:07
PHST- 2023/09/07 00:00 [received]
PHST- 2023/11/27 00:00 [accepted]
PHST- 2024/03/04 06:43 [medline]
PHST- 2023/12/16 11:43 [pubmed]
PHST- 2023/12/16 00:07 [entrez]
AID - 7475815 [pii]
AID - 10.1093/jb/mvad105 [doi]
PST - ppublish
SO  - J Biochem. 2024 Mar 4;175(3):313-322. doi: 10.1093/jb/mvad105.