APN-mediated phosphorylation of BCKDK promotes hepatocellular carcinoma metastasis and proliferation via the ERK signaling pathway.

Animals Base Sequence CD13 Antigens / metabolism Carcinoma, Hepatocellular / genetics Cell Line, Tumor Cell Proliferation Disease Progression Female Gene Expression Regulation, Neoplastic Humans Liver Neoplasms / genetics MAP Kinase Signaling System Mice, Inbred NOD Mice, SCID Neoplasm Metastasis Phosphorylation Phosphoserine / metabolism Protein Binding Protein Kinases / metabolism Up-Regulation / genetics

Journal

Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092

Informations de publication

Date de publication:
26 05 2020
Historique:
received: 28 12 2019
accepted: 14 05 2020
revised: 13 05 2020
entrez: 28 5 2020
pubmed: 28 5 2020
medline: 13 3 2021
Statut: epublish

Résumé

Hepatocellular carcinoma (HCC) is one of the most prevalent human malignancies worldwide and has high morbidity and mortality. Elucidating the molecular mechanisms underlying HCC recurrence and metastasis is critical to identify new therapeutic targets. This study aimed to determine the roles of aminopeptidase N (APN, also known as CD13) in HCC proliferation and metastasis and its underlying mechanisms. We detected APN expression in clinical samples and HCC cell lines using immunohistochemistry, flow cytometry, real-time PCR, and enzyme activity assays. The effects of APN on HCC metastasis and proliferation were verified in both in vitro and in vivo models. RNA-seq, phosphoproteomic, western blot, point mutation, co-immunoprecipitation, and proximity ligation assays were performed to reveal the potential mechanisms. We found that APN was frequently upregulated in HCC tumor tissues and high-metastatic cell lines. Knockout of APN inhibited HCC cell metastasis and proliferation in vitro and in vivo. Functional studies suggested that a loss of APN impedes the ERK signaling pathway in HCC cells. Mechanistically, we found that APN might mediate the phosphorylation at serine 31 of BCKDK (BCKDK

Identifiants

DOI: 10.1038/s41419-020-2610-1 PMID: 32457292 PMC: PMC7249043
pubmed: 32457292
doi: 10.1038/s41419-020-2610-1
pii: 10.1038/s41419-020-2610-1
pmc: PMC7249043
doi:

Substances chimiques

Phosphoserine 17885-08-4
Protein Kinases EC 2.7.-
(3-methyl-2-oxobutanoate dehydrogenase (lipoamide)) kinase EC 2.7.11.4
CD13 Antigens EC 3.4.11.2

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

396

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Auteurs

Mengying Zhai (M)

Department of Immunology, Key Laboratory of Immune Microenvironment and Disease of the Educational Ministry of China, Tianjin Key Laboratory of Cellular and Molecular Immunology, School of Basic Medical Sciences, Tianjin Medical University, 300070, Tianjin, China.
ORCID: 0000-0001-9340-1900

Zixia Yang (Z)

Department of Immunology, Key Laboratory of Immune Microenvironment and Disease of the Educational Ministry of China, Tianjin Key Laboratory of Cellular and Molecular Immunology, School of Basic Medical Sciences, Tianjin Medical University, 300070, Tianjin, China.

Chenrui Zhang (C)

Department of Immunology, Key Laboratory of Immune Microenvironment and Disease of the Educational Ministry of China, Tianjin Key Laboratory of Cellular and Molecular Immunology, School of Basic Medical Sciences, Tianjin Medical University, 300070, Tianjin, China.

Jinping Li (J)

Department of Immunology, Key Laboratory of Immune Microenvironment and Disease of the Educational Ministry of China, Tianjin Key Laboratory of Cellular and Molecular Immunology, School of Basic Medical Sciences, Tianjin Medical University, 300070, Tianjin, China.
Tianjin Kangzhe Pharmaceutical Technology Development Company, Ltd., 300042, Tianjin, China.

Jing Jia (J)

Department of Immunology, Key Laboratory of Immune Microenvironment and Disease of the Educational Ministry of China, Tianjin Key Laboratory of Cellular and Molecular Immunology, School of Basic Medical Sciences, Tianjin Medical University, 300070, Tianjin, China.
Tianjin Kangzhe Pharmaceutical Technology Development Company, Ltd., 300042, Tianjin, China.

Lingyi Zhou (L)

Department of Immunology, Key Laboratory of Immune Microenvironment and Disease of the Educational Ministry of China, Tianjin Key Laboratory of Cellular and Molecular Immunology, School of Basic Medical Sciences, Tianjin Medical University, 300070, Tianjin, China.

Rong Lu (R)

Tianjin Kangzhe Pharmaceutical Technology Development Company, Ltd., 300042, Tianjin, China. lu_rong@vip.sina.com.

Zhi Yao (Z)

Department of Immunology, Key Laboratory of Immune Microenvironment and Disease of the Educational Ministry of China, Tianjin Key Laboratory of Cellular and Molecular Immunology, School of Basic Medical Sciences, Tianjin Medical University, 300070, Tianjin, China. yaozhi@tmu.edu.cn.
2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Medical University, 300070, Tianjin, China. yaozhi@tmu.edu.cn.

Zheng Fu (Z)

Department of Immunology, Key Laboratory of Immune Microenvironment and Disease of the Educational Ministry of China, Tianjin Key Laboratory of Cellular and Molecular Immunology, School of Basic Medical Sciences, Tianjin Medical University, 300070, Tianjin, China. fuzhengcn@vip.sina.com.
Tianjin Kangzhe Pharmaceutical Technology Development Company, Ltd., 300042, Tianjin, China. fuzhengcn@vip.sina.com.
ORCID: 0000-0002-7483-832X

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › APN-mediated phosphorylation of BCKDK promotes...
questionsmedicales.fr › Sciences de l'information › Sources d'information › Services d'information › Documentation › Données de séquences moléculaires › Séquence nucléotidique › APN-mediated phosphorylation of BCKDK promotes...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Antigènes de différenciation › Antigènes de différenciation des lymphocytes T › Antigènes CD13 › APN-mediated phosphorylation of BCKDK promotes...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies du foie › Tumeurs du foie › Carcinome hépatocellulaire › APN-mediated phosphorylation of BCKDK promotes...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › APN-mediated phosphorylation of BCKDK promotes...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Croissance › Processus de croissance cellulaire › Prolifération cellulaire › APN-mediated phosphorylation of BCKDK promotes...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Évolution de la maladie › APN-mediated phosphorylation of BCKDK promotes...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes tumoraux › APN-mediated phosphorylation of BCKDK promotes...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › APN-mediated phosphorylation of BCKDK promotes...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies du foie › Tumeurs du foie › APN-mediated phosphorylation of BCKDK promotes...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Système de signalisation des MAP kinases › APN-mediated phosphorylation of BCKDK promotes...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée NOD › APN-mediated phosphorylation of BCKDK promotes...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souches mutantes de souris › Souris SCID › APN-mediated phosphorylation of BCKDK promotes...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Processus néoplasiques › Métastase tumorale › APN-mediated phosphorylation of BCKDK promotes...
questionsmedicales.fr › Métabolisme › Phosphorylation › APN-mediated phosphorylation of BCKDK promotes...
questionsmedicales.fr › Acides aminés, peptides et protéines › Acides aminés › Acides phosphoaminés › Phosphosérine › APN-mediated phosphorylation of BCKDK promotes...
questionsmedicales.fr › Métabolisme › Liaison aux protéines › APN-mediated phosphorylation of BCKDK promotes...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › Phosphotransferases › Phosphotransferases (Alcohol Group Acceptor) › Protein kinases › APN-mediated phosphorylation of BCKDK promotes...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Régulation positive › APN-mediated phosphorylation of BCKDK promotes...