Glutathione peroxidase 2 knockdown suppresses gastric cancer progression and metastasis via regulation of kynurenine metabolism.

Humans Stomach Neoplasms / pathology Kynurenine / metabolism Reactive Oxygen Species / metabolism Proteomics Tryptophan / metabolism Cell Line, Tumor Glutathione Peroxidase / genetics Epithelial-Mesenchymal Transition / genetics Gene Expression Regulation, Neoplastic Cell Movement / genetics Cell Proliferation / genetics

Journal

Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562

Informations de publication

Date de publication:
Jun 2023
Historique:
received: 14 11 2022
accepted: 21 04 2023
revised: 19 04 2023
medline: 12 6 2023
pubmed: 4 5 2023
entrez: 3 5 2023
Statut: ppublish

Résumé

Gastric cancer (GC) is among the most lethal malignancies due to its poor early diagnosis and high metastasis rate, and new therapeutic targets are urgently needed to develop effective anti-GC drugs. Glutathione peroxidase-2 (GPx2) plays various roles in tumor progression and patient survival. Herein, we found that GPx2 was overexpressed and negatively correlated with poor prognosis by using clinical GC samples for validation. GPx2 knockdown suppressed GC proliferation, invasion, migration and epithelial-mesenchymal transition (EMT) in vitro and in vivo. In addition, proteomic analysis revealed that GPx2 expression regulated kynureninase (KYNU)-mediated metabolism. As one of the key proteins involved in tryptophan catabolism, KYNU can degrade the tryptophan metabolite kynurenine (kyn), which is an endogenous ligand for AhR. Next, we revealed that the activation of the reactive oxygen species (ROS)-mediated KYNU-kyn-AhR signaling pathway caused by GPx2 knockdown was involved in GC progression and metastasis. In conclusion, our results showed that GPx2 acted as an oncogene in GC and that GPx2 knockdown suppressed GC progression and metastasis by suppressing the KYNU-kyn-AhR signaling pathway, which was caused by the accumulation of ROS.

Identifiants

DOI: 10.1038/s41388-023-02708-4 PMID: 37138031 PMC: PMC10256612
pubmed: 37138031
doi: 10.1038/s41388-023-02708-4
pii: 10.1038/s41388-023-02708-4
pmc: PMC10256612
doi:

Substances chimiques

Kynurenine 343-65-7
Reactive Oxygen Species 0
Tryptophan 8DUH1N11BX
Glutathione Peroxidase EC 1.11.1.9

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1994-2006

Subventions

Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 82074245, 81973634, 81903842
Organisme : Natural Science Foundation of Zhejiang Province (Zhejiang Provincial Natural Science Foundation)
ID : LR21H280001

Informations de copyright

© 2023. The Author(s).

Références

Theranostics. 2019 Oct 21;9(26):8294-8311
pubmed: 31754397
Mol Cancer. 2022 Mar 10;21(1):70
pubmed: 35272681
Nature. 2011 Oct 05;478(7368):197-203
pubmed: 21976023
Front Nutr. 2021 Aug 11;8:712327
pubmed: 34458309
Am J Cancer Res. 2022 Jun 15;12(6):2558-2575
pubmed: 35812057
Oncogene. 2018 Nov;37(44):5843-5857
pubmed: 29980787
Front Pharmacol. 2022 May 17;13:911663
pubmed: 35656301
Cell. 2020 Sep 3;182(5):1252-1270.e34
pubmed: 32818467
J Cell Mol Med. 2021 Mar;25(5):2309-2314
pubmed: 33486887
Oncol Rep. 2022 Dec;48(6):
pubmed: 36222298
Oncoimmunology. 2022 Mar 25;11(1):2055703
pubmed: 35355679
J Cell Physiol. 2020 Nov;235(11):7780-7790
pubmed: 31774184
Lancet. 2010 Aug 28;376(9742):687-97
pubmed: 20728210
J Oncol. 2022 Jun 15;2022:6065516
pubmed: 35756080
World J Urol. 2015 Nov;33(11):1777-89
pubmed: 25813210
Nucleic Acids Res. 2017 Jul 3;45(W1):W98-W102
pubmed: 28407145
Cancer Sci. 2022 Jan;113(1):170-181
pubmed: 34714577
J Pers Med. 2022 Jul 25;12(8):
pubmed: 35893303
Theranostics. 2021 Mar 4;11(10):4839-4857
pubmed: 33754031
Oncotarget. 2016 Aug 2;7(31):49322-49333
pubmed: 27384994
Toxicol Appl Pharmacol. 2017 May 1;322:75-88
pubmed: 28284859
Proc Natl Acad Sci U S A. 2022 Feb 22;119(8):
pubmed: 35193955
Cancer Biomark. 2017 Jul 4;19(3):335-340
pubmed: 28453466
Oncogene. 2020 Feb;39(8):1619-1633
pubmed: 31723239
Cancer Cell. 2018 Mar 12;33(3):480-494.e7
pubmed: 29533786
Transl Neurosci. 2021 Jan 20;12(1):32-39
pubmed: 33552592
BMC Cancer. 2016 Jul 07;16:410
pubmed: 27388201
CA Cancer J Clin. 2021 May;71(3):209-249
pubmed: 33538338
Sci Transl Med. 2015 Oct 7;7(308):308re8
pubmed: 26446958
Ann Transl Med. 2020 Jun;8(11):678
pubmed: 32617298
Nat Rev Cancer. 2022 May;22(5):280-297
pubmed: 35102280
Nat Commun. 2019 Sep 27;10(1):4397
pubmed: 31562301
Signal Transduct Target Ther. 2020 Feb 21;5(1):10
pubmed: 32296044
Cancers (Basel). 2020 Jan 07;12(1):
pubmed: 31936153
Cancer Cell. 2020 Aug 10;38(2):167-197
pubmed: 32649885
Cancers (Basel). 2020 Aug 06;12(8):
pubmed: 32781581
Cancer Res. 2017 Nov 1;77(21):5769-5781
pubmed: 28916653
Pharmacol Res. 2021 Mar;165:105411
pubmed: 33401002
Lancet. 2016 Nov 26;388(10060):2654-2664
pubmed: 27156933
Carcinogenesis. 2014 Sep;35(9):1962-7
pubmed: 24562575
Free Radic Biol Med. 2022 Aug 1;188:419-433
pubmed: 35803440

Auteurs

Handong Xu (H)

Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, China.
First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310053, China.

Can Hu (C)

Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, China.
Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou, 310022, China.
Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, 310022, China.

Yi Wang (Y)

Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, China.
First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310053, China.

Yunfu Shi (Y)

Tongde Hospital of Zhejiang Province, Hangzhou, China.
Key Laboratory of Cancer Prevention and Therapy Combining Traditional Chinese and Western Medicine of Zhejiang Province, Hangzhou, China.

Li Yuan (L)

Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, China.
Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou, 310022, China.
Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, 310022, China.

Jingli Xu (J)

Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, China.
First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou, 310022, China.
Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, 310022, China.

Yanqiang Zhang (Y)

Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, China.
Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou, 310022, China.
Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, 310022, China.

Jiahui Chen (J)

Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, China.
Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou, 310022, China.
Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, 310022, China.

Qin Wei (Q)

Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, China.
Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou, 310022, China.
Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, 310022, China.

Jiangjiang Qin (J)

Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, China. jqin@zcmu.edu.cn.
Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou, 310022, China. jqin@zcmu.edu.cn.
Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, 310022, China. jqin@zcmu.edu.cn.
ORCID: 0000-0002-8559-616X

Zhiyuan Xu (Z)

Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, China. xuzy@zjcc.org.cn.
Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou, 310022, China. xuzy@zjcc.org.cn.
Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, 310022, China. xuzy@zjcc.org.cn.

Xiangdong Cheng (X)

Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, China. chengxd@zjcc.org.cn.
Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou, 310022, China. chengxd@zjcc.org.cn.
Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, 310022, China. chengxd@zjcc.org.cn.
ORCID: 0000-0002-5099-490X

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Glutathione peroxidase 2 knockdown suppresses...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies gastro-intestinales › Maladies de l'estomac › Tumeurs de l'estomac › Glutathione peroxidase 2 knockdown suppresses...
questionsmedicales.fr › Acides aminés, peptides et protéines › Acides aminés › Cynurénine › Glutathione peroxidase 2 knockdown suppresses...
questionsmedicales.fr › Produits chimiques inorganiques › Composés de l'oxygène › Espèces réactives de l'oxygène › Glutathione peroxidase 2 knockdown suppresses...
questionsmedicales.fr › Disciplines des sciences naturelles › Chimie › Biochimie › Protéomique › Glutathione peroxidase 2 knockdown suppresses...
questionsmedicales.fr › Acides aminés, peptides et protéines › Acides aminés › Acides aminés essentiels › Tryptophane › Glutathione peroxidase 2 knockdown suppresses...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Glutathione peroxidase 2 knockdown suppresses...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Sélénoprotéines › Glutathione peroxidase › Glutathione peroxidase 2 knockdown suppresses...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transdifférenciation cellulaire › Transition épithélio-mésenchymateuse › Glutathione peroxidase 2 knockdown suppresses...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes tumoraux › Glutathione peroxidase 2 knockdown suppresses...
questionsmedicales.fr › Phénomènes physiologiques › Mouvement cellulaire › Glutathione peroxidase 2 knockdown suppresses...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Croissance › Processus de croissance cellulaire › Prolifération cellulaire › Glutathione peroxidase 2 knockdown suppresses...