Bulk and single-cell transcriptome profiling reveal extracellular matrix mechanical regulation of lipid metabolism reprograming through YAP/TEAD4/ACADL axis in hepatocellular carcinoma.

Humans Carcinoma, Hepatocellular / metabolism Liver Neoplasms / metabolism Lipid Metabolism / genetics Acyl-CoA Dehydrogenase / genetics Adaptor Proteins, Signal Transducing / metabolism YAP-Signaling Proteins Cell Line, Tumor Phosphoproteins / metabolism Transcription Factors / genetics Gene Expression Profiling Gene Expression Regulation, Neoplastic / genetics TEA Domain Transcription Factors
ACADL Hepatocellular carcinoma YAP extracellular matrix

Journal

International journal of biological sciences
ISSN: 1449-2288
Titre abrégé: Int J Biol Sci
Pays: Australia
ID NLM: 101235568

Informations de publication

Date de publication:
2023
Historique:
received: 27 12 2022
accepted: 22 03 2023
medline: 9 5 2023
pubmed: 8 5 2023
entrez: 8 5 2023
Statut: epublish

Résumé

Emerging studies have revealed matrix stiffness promotes hepatocellular carcinoma (HCC) development. We studied metabolic dysregulation in HCC using the TCGA-LIHC database (n=374) and GEO datasets (GSE14520). HCC samples were classified into three heterogeneous metabolic pathway subtypes with different metabolic profiles: Cluster 1, an ECM-producing subtype with upregulated glycan metabolism; Cluster 2, a hybrid subtype with partial pathway dysregulation. Cluster 3, a lipogenic subtype with upregulated lipid metabolism; These three subtypes have different prognosis, clinical features and genomic alterations. We identified key enzymes that respond to matrix stiffness and regulate lipid metabolism through bioinformatic analysis. We found long-chain acyl-CoA dehydrogenase (ACADL) is a mechanoreactive enzyme that reprograms HCC cell lipid metabolism in response to extracellular matrix stiffness. ACADL is also regarded as tumor suppressor in HCC. We found that increased extracellular matrix stiffness led to activation of Yes-associated protein (YAP) and the YAP/TEA Domain transcription factor 4 (TEAD4) transcriptional complex was able to directly repress ACADL at the transcriptional level. The ACADL-dependent mechanoresponsive pathway is a potential therapeutic target for HCC treatment.

Identifiants

DOI: 10.7150/ijbs.82177 PMID: 37151879 PMC: PMC10158031
pubmed: 37151879
doi: 10.7150/ijbs.82177
pii: ijbsv19p2114
pmc: PMC10158031
doi:

Substances chimiques

Acyl-CoA Dehydrogenase EC 1.3.8.7
Adaptor Proteins, Signal Transducing 0
YAP-Signaling Proteins 0
Phosphoproteins 0
Transcription Factors 0
TEAD4 protein, human 0
TEA Domain Transcription Factors 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

2114-2131

Informations de copyright

© The author(s).

Déclaration de conflit d'intérêts

Competing Interests: The authors have declared that no competing interest exists.

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Auteurs

Jingwei Cai (J)

Key Laboratory of Laparoscopic Technology of Zhejiang Province, Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, 310016, Hangzhou, China.
Zhejiang Minimal Invasive Diagnosis and Treatment Technology Research Center of Severe Hepatobiliary Disease, Zhejiang Research and Development Engineering Laboratory of Minimally Invasive Technology and Equipment 310016, Hangzhou, China.
Zhejiang University Cancer Center, 310058, Hangzhou, China.
Liangzhu Laboratory, Zhejiang University Medical Center, 311121, Hangzhou, China.

Tianyi Chen (T)

Key Laboratory of Laparoscopic Technology of Zhejiang Province, Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, 310016, Hangzhou, China.
Zhejiang Minimal Invasive Diagnosis and Treatment Technology Research Center of Severe Hepatobiliary Disease, Zhejiang Research and Development Engineering Laboratory of Minimally Invasive Technology and Equipment 310016, Hangzhou, China.
Zhejiang University Cancer Center, 310058, Hangzhou, China.
Liangzhu Laboratory, Zhejiang University Medical Center, 311121, Hangzhou, China.

Zhiyu Jiang (Z)

Key Laboratory of Laparoscopic Technology of Zhejiang Province, Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, 310016, Hangzhou, China.
Zhejiang Minimal Invasive Diagnosis and Treatment Technology Research Center of Severe Hepatobiliary Disease, Zhejiang Research and Development Engineering Laboratory of Minimally Invasive Technology and Equipment 310016, Hangzhou, China.
Zhejiang University Cancer Center, 310058, Hangzhou, China.
Liangzhu Laboratory, Zhejiang University Medical Center, 311121, Hangzhou, China.

Jiafei Yan (J)

Key Laboratory of Laparoscopic Technology of Zhejiang Province, Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, 310016, Hangzhou, China.
Zhejiang Minimal Invasive Diagnosis and Treatment Technology Research Center of Severe Hepatobiliary Disease, Zhejiang Research and Development Engineering Laboratory of Minimally Invasive Technology and Equipment 310016, Hangzhou, China.
Zhejiang University Cancer Center, 310058, Hangzhou, China.
Liangzhu Laboratory, Zhejiang University Medical Center, 311121, Hangzhou, China.

Zhengtao Ye (Z)

Key Laboratory of Laparoscopic Technology of Zhejiang Province, Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, 310016, Hangzhou, China.
Zhejiang Minimal Invasive Diagnosis and Treatment Technology Research Center of Severe Hepatobiliary Disease, Zhejiang Research and Development Engineering Laboratory of Minimally Invasive Technology and Equipment 310016, Hangzhou, China.
Zhejiang University Cancer Center, 310058, Hangzhou, China.
Liangzhu Laboratory, Zhejiang University Medical Center, 311121, Hangzhou, China.

Yeling Ruan (Y)

Key Laboratory of Laparoscopic Technology of Zhejiang Province, Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, 310016, Hangzhou, China.
Zhejiang Minimal Invasive Diagnosis and Treatment Technology Research Center of Severe Hepatobiliary Disease, Zhejiang Research and Development Engineering Laboratory of Minimally Invasive Technology and Equipment 310016, Hangzhou, China.
Zhejiang University Cancer Center, 310058, Hangzhou, China.
Liangzhu Laboratory, Zhejiang University Medical Center, 311121, Hangzhou, China.

Liye Tao (L)

Key Laboratory of Laparoscopic Technology of Zhejiang Province, Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, 310016, Hangzhou, China.
Zhejiang Minimal Invasive Diagnosis and Treatment Technology Research Center of Severe Hepatobiliary Disease, Zhejiang Research and Development Engineering Laboratory of Minimally Invasive Technology and Equipment 310016, Hangzhou, China.
Zhejiang University Cancer Center, 310058, Hangzhou, China.
Liangzhu Laboratory, Zhejiang University Medical Center, 311121, Hangzhou, China.

Zefeng Shen (Z)

Key Laboratory of Laparoscopic Technology of Zhejiang Province, Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, 310016, Hangzhou, China.
Zhejiang Minimal Invasive Diagnosis and Treatment Technology Research Center of Severe Hepatobiliary Disease, Zhejiang Research and Development Engineering Laboratory of Minimally Invasive Technology and Equipment 310016, Hangzhou, China.
Zhejiang University Cancer Center, 310058, Hangzhou, China.
Liangzhu Laboratory, Zhejiang University Medical Center, 311121, Hangzhou, China.

Xiao Liang (X)

Key Laboratory of Laparoscopic Technology of Zhejiang Province, Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, 310016, Hangzhou, China.
Zhejiang Minimal Invasive Diagnosis and Treatment Technology Research Center of Severe Hepatobiliary Disease, Zhejiang Research and Development Engineering Laboratory of Minimally Invasive Technology and Equipment 310016, Hangzhou, China.
Zhejiang University Cancer Center, 310058, Hangzhou, China.
Liangzhu Laboratory, Zhejiang University Medical Center, 311121, Hangzhou, China.

Yifan Wang (Y)

Key Laboratory of Laparoscopic Technology of Zhejiang Province, Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, 310016, Hangzhou, China.
Zhejiang Minimal Invasive Diagnosis and Treatment Technology Research Center of Severe Hepatobiliary Disease, Zhejiang Research and Development Engineering Laboratory of Minimally Invasive Technology and Equipment 310016, Hangzhou, China.
Zhejiang University Cancer Center, 310058, Hangzhou, China.
Liangzhu Laboratory, Zhejiang University Medical Center, 311121, Hangzhou, China.

Junjie Xu (J)

Key Laboratory of Laparoscopic Technology of Zhejiang Province, Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, 310016, Hangzhou, China.
Zhejiang Minimal Invasive Diagnosis and Treatment Technology Research Center of Severe Hepatobiliary Disease, Zhejiang Research and Development Engineering Laboratory of Minimally Invasive Technology and Equipment 310016, Hangzhou, China.
Zhejiang University Cancer Center, 310058, Hangzhou, China.
Liangzhu Laboratory, Zhejiang University Medical Center, 311121, Hangzhou, China.

Xiujun Cai (X)

Key Laboratory of Laparoscopic Technology of Zhejiang Province, Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, 310016, Hangzhou, China.
Zhejiang Minimal Invasive Diagnosis and Treatment Technology Research Center of Severe Hepatobiliary Disease, Zhejiang Research and Development Engineering Laboratory of Minimally Invasive Technology and Equipment 310016, Hangzhou, China.
Zhejiang University Cancer Center, 310058, Hangzhou, China.
Liangzhu Laboratory, Zhejiang University Medical Center, 311121, Hangzhou, China.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Bulk and single-cell transcriptome profiling...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies du foie › Tumeurs du foie › Carcinome hépatocellulaire › Bulk and single-cell transcriptome profiling...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies du foie › Tumeurs du foie › Bulk and single-cell transcriptome profiling...
questionsmedicales.fr › Métabolisme › Métabolisme lipidique › Bulk and single-cell transcriptome profiling...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Flavoprotéines › Acyl-CoA dehydrogenase › Bulk and single-cell transcriptome profiling...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protéines adaptatrices de la transduction du signal › Bulk and single-cell transcriptome profiling...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protéines adaptatrices de la transduction du signal › Protéines de signalisation YAP › Bulk and single-cell transcriptome profiling...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Bulk and single-cell transcriptome profiling...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Phosphoprotéines › Bulk and single-cell transcriptome profiling...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Bulk and single-cell transcriptome profiling...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de profil d'expression de gènes › Bulk and single-cell transcriptome profiling...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes tumoraux › Bulk and single-cell transcriptome profiling...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription à domaine TEA › Bulk and single-cell transcriptome profiling...