AMER1 deficiency promotes the distant metastasis of colorectal cancer by inhibiting SLC7A11- and FTL-mediated ferroptosis.

Humans Apoferritins Ferroptosis Colonic Neoplasms Cross Reactions Cystine Colorectal Neoplasms / genetics Amino Acid Transport System y+ / genetics Tumor Suppressor Proteins Adaptor Proteins, Signal Transducing
AMER1 CP: Cancer FTL SLC7A11 colorectal cancer ferroptosis metastasis

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
26 09 2023
Historique:
received: 24 01 2023
revised: 21 07 2023
accepted: 24 08 2023
medline: 5 10 2023
pubmed: 8 9 2023
entrez: 8 9 2023
Statut: ppublish

Résumé

The crosstalk between ferroptosis and cancer metastasis remains unclear. Here, we identify AMER1 as a key regulator of ferroptosis. AMER1 loss causes resistance to ferroptosis in colorectal cancer (CRC) cells. Interestingly, AMER1-deficient CRC cells preferentially form distant metastases, while AMER1-naive CRC cells mainly invade lymph nodes. Moreover, the ferroptosis inhibitor liproxstatin-1 effectively promotes hematogenous transfer of AMER1-naive cells. Mechanistically, AMER1 binds to SLC7A11 and ferritin light chain (FTL) and recruits β-TrCP1/2, which degrade SLC7A11 and FTL by ubiquitination. Therefore, AMER1 deficiency increases cellular cystine levels but decreases the pool of labile free iron, thereby enhancing resistance to ferroptosis in CRC cells. Thus, AMER1 deficiency increases the survival of CRC cells in the blood under conditions of high oxidative stress and then promotes hematogenous metastasis of CRC. In conclusion, AMER1 mediates the crosstalk between ferroptosis and cancer metastasis, which provides a window of opportunity for treating metastatic colorectal cancer patients with AMER1 mutations.

Identifiants

DOI: 10.1016/j.celrep.2023.113110 PMID: 37682704
pubmed: 37682704
pii: S2211-1247(23)01121-X
doi: 10.1016/j.celrep.2023.113110
pii:
doi:

Substances chimiques

Apoferritins 9013-31-4
Cystine 48TCX9A1VT
SLC7A11 protein, human 0
Amino Acid Transport System y+ 0
FTL protein, human 0
AMER1 protein, human 0
Tumor Suppressor Proteins 0
Adaptor Proteins, Signal Transducing 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

113110

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no conflict of interest.

Auteurs

Siqin Lei (S)

Department of Pathology and International Institutes of Medicine, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Research Unit of Intelligence Classification of Tumor Pathology and Precision Therapy, Chinese Academy of Medical Sciences (2019RU042), Hangzhou 310058, China.

Chaoyi Chen (C)

Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, Zhejiang Provincial Clinical Research Center for Cancer, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Cancer Center, Zhejiang University, Hangzhou, Zhejiang 310058, China.

Fengyan Han (F)

Department of Pathology and International Institutes of Medicine, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Research Unit of Intelligence Classification of Tumor Pathology and Precision Therapy, Chinese Academy of Medical Sciences (2019RU042), Hangzhou 310058, China.

Jingwen Deng (J)

Department of Pathology and International Institutes of Medicine, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Research Unit of Intelligence Classification of Tumor Pathology and Precision Therapy, Chinese Academy of Medical Sciences (2019RU042), Hangzhou 310058, China.

Dongdong Huang (D)

The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China.

Lili Qian (L)

Cancer Center, Department of Pathology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang 310014, China.

Ming Zhu (M)

Department of Pathology and International Institutes of Medicine, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Research Unit of Intelligence Classification of Tumor Pathology and Precision Therapy, Chinese Academy of Medical Sciences (2019RU042), Hangzhou 310058, China.

Xiaohui Ma (X)

Pharmacology & Toxicology Research Center, The State Key Laboratory of Core Technology in Innovative Chinese Medicine, Tasly Academy, Tasly Holding Group Co., Ltd., Tianjin 300410, China.

Maode Lai (M)

Department of Pathology, Zhejiang University School of Medicine, Research Unit of Intelligence Classification of Tumor Pathology and Precision Therapy of the Chinese Academy of Medical Sciences (2019RU042), Hangzhou 310058, China; Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang University, Hangzhou 310058, China.

Enping Xu (E)

Department of Pathology, Zhejiang University School of Medicine, Research Unit of Intelligence Classification of Tumor Pathology and Precision Therapy of the Chinese Academy of Medical Sciences (2019RU042), Hangzhou 310058, China; Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang University, Hangzhou 310058, China. Electronic address: xep@zju.edu.cn.

Honghe Zhang (H)

Department of Pathology and International Institutes of Medicine, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Research Unit of Intelligence Classification of Tumor Pathology and Precision Therapy, Chinese Academy of Medical Sciences (2019RU042), Hangzhou 310058, China; Key Laboratory of Disease Proteomics of Zhejiang Province, Zhejiang University, Hangzhou 310058, China. Electronic address: honghezhang@zju.edu.cn.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › AMER1 deficiency promotes the distant...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Métalloprotéines › Protéines de liaison au fer › Ferritines › Apoferritines › AMER1 deficiency promotes the distant...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Mort cellulaire › Mort cellulaire régulée › Ferroptose › AMER1 deficiency promotes the distant...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies gastro-intestinales › Maladies intestinales › Tumeurs de l'intestin › Tumeurs du côlon › AMER1 deficiency promotes the distant...
questionsmedicales.fr › Phénomènes du système immunitaire › Réaction antigène-anticorps › Réactions croisées › AMER1 deficiency promotes the distant...
questionsmedicales.fr › Acides aminés, peptides et protéines › Acides aminés › Acides aminés soufrés › Cystéine › Cystine › AMER1 deficiency promotes the distant...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies gastro-intestinales › Maladies intestinales › Maladies du rectum › Tumeurs colorectales › AMER1 deficiency promotes the distant...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › Protéines transporteurs de solutés › Système y+ de transport d'acides aminés › AMER1 deficiency promotes the distant...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines suppresseurs de tumeurs › AMER1 deficiency promotes the distant...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protéines adaptatrices de la transduction du signal › AMER1 deficiency promotes the distant...