PMID- 37878531
OWN - NLM
STAT- MEDLINE
DCOM- 20240130
LR  - 20240206
IS  - 1349-7006 (Electronic)
IS  - 1347-9032 (Print)
IS  - 1347-9032 (Linking)
VI  - 115
IP  - 1
DP  - 2024 Jan
TI  - Impact of TP53-induced glycolysis and apoptosis regulator on malignant activity 
      and resistance to ferroptosis in intrahepatic cholangiocarcinoma.
PG  - 170-183
LID - 10.1111/cas.15981 [doi]
AB  - TP53-induced glycolysis and apoptosis regulator (TIGAR) is an important gene that 
      encodes a regulatory enzyme of glycolysis and reactive oxygen species (ROS) 
      detoxification and is associated with worse prognosis in various cancers. 
      Ferroptosis is a recently identified type of programmed cell death that is 
      triggered by iron-dependent lipid peroxidation. There are no reports on the 
      prognostic impact of TIGAR on intrahepatic cholangiocarcinoma (ICC), and its role 
      in ferroptosis is unclear. Ninety ICC patients who had undergone hepatic 
      resection were enrolled. Immunohistochemical staining for TIGAR was performed. 
      The regulation of malignant activity by TIGAR and the association between 
      ferroptosis and TIGAR were investigated in vitro. Twenty-two (24.4%) patients 
      were categorized into TIGAR-high and -low groups by immunohistochemical staining. 
      There were no noticeable differences in background factors between the two 
      groups, but TIGAR positivity was an independent prognostic factor in disease-free 
      survival (hazard ratio [HR], 2.00; 95% confidence interval [CI], 1.04-3.85, 
      p = 0.0378) and overall survival (HR, 2.10; 95% CI, 1.03-4.30, p = 0.00422) in a 
      multivariate analysis. In vitro, TIGAR knockdown (KD) decreased cell motility 
      (cell proliferation/migration/invasion/colony-forming capabilities) and elevated 
      ROS and lipid peroxidation. This indicated that TIGAR KD induced ferroptosis. 
      TIGAR KD-induced ferroptosis was suppressed using liproxstatin. TIGAR KD 
      decreased the expression of glutathione peroxidase 4, known as factor-suppressing 
      ferroptosis. The combination of TIGAR KD with cisplatin significantly induced 
      more ferroptosis. In conclusion, TIGAR is associated with poor outcomes in ICC 
      patients and resistance to ferroptosis.
CI  - (c) 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd 
      on behalf of Japanese Cancer Association.
FAU - Toshida, Katsuya
AU  - Toshida K
AD  - Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, Japan.
FAU - Itoh, Shinji
AU  - Itoh S
AUID- ORCID: 0000-0003-0382-2520
AD  - Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, Japan.
FAU - Iseda, Norifumi
AU  - Iseda N
AD  - Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, Japan.
FAU - Izumi, Takuma
AU  - Izumi T
AD  - Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, Japan.
FAU - Yoshiya, Shohei
AU  - Yoshiya S
AD  - Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, Japan.
FAU - Toshima, Takeo
AU  - Toshima T
AUID- ORCID: 0000-0003-4019-8288
AD  - Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, Japan.
FAU - Ninomiya, Mizuki
AU  - Ninomiya M
AD  - Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, Japan.
FAU - Iwasaki, Takeshi
AU  - Iwasaki T
AD  - Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, Japan.
FAU - Oda, Yoshinao
AU  - Oda Y
AUID- ORCID: 0000-0001-9636-1182
AD  - Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, Japan.
FAU - Yoshizumi, Tomoharu
AU  - Yoshizumi T
AD  - Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, Japan.
LA  - eng
GR  - JP-19K09198/Japan Society for the Promotion of Science/
GR  - JP-23K08133/Japan Society for the Promotion of Science/
GR  - the Kobayashi Foundation for Cancer Research/
GR  - the Takeda Science Foundation/
PT  - Journal Article
DEP - 20231025
PL  - England
TA  - Cancer Sci
JT  - Cancer science
JID - 101168776
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - EC 3.1.3.2 (Phosphoric Monoester Hydrolases)
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (TP53 protein, human)
RN  - 0 (Tumor Suppressor Protein p53)
SB  - IM
MH  - Humans
MH  - Reactive Oxygen Species/metabolism
MH  - Intracellular Signaling Peptides and Proteins/metabolism
MH  - *Ferroptosis
MH  - Phosphoric Monoester Hydrolases
MH  - Apoptosis Regulatory Proteins/genetics
MH  - Apoptosis/genetics
MH  - Glycolysis/genetics
MH  - *Cholangiocarcinoma/genetics
MH  - Tumor Suppressor Protein p53/metabolism
PMC - PMC10823267
OTO - NOTNLM
OT  - TP53-induced glycolysis and apoptosis regulator
OT  - cisplatin
OT  - ferroptosis
OT  - intrahepatic cholangiocarcinoma
COIS- Y.O. is an Editorial Board Member of Cancer Science. The other authors have no 
      conflict of interest.
EDAT- 2023/10/25 18:42
MHDA- 2024/01/30 12:42
PMCR- 2023/10/25
CRDT- 2023/10/25 13:13
PHST- 2023/09/12 00:00 [revised]
PHST- 2023/07/13 00:00 [received]
PHST- 2023/09/15 00:00 [accepted]
PHST- 2024/01/30 12:42 [medline]
PHST- 2023/10/25 18:42 [pubmed]
PHST- 2023/10/25 13:13 [entrez]
PHST- 2023/10/25 00:00 [pmc-release]
AID - CAS15981 [pii]
AID - 10.1111/cas.15981 [doi]
PST - ppublish
SO  - Cancer Sci. 2024 Jan;115(1):170-183. doi: 10.1111/cas.15981. Epub 2023 Oct 25.