Aberrant (pro)renin receptor expression induces genomic instability in pancreatic ductal adenocarcinoma through upregulation of SMARCA5/SNF2H.

Adenosine Triphosphatases / genetics Animals Carcinoma, Pancreatic Ductal / genetics Cell Line Cell Transformation, Neoplastic Chromatin Assembly and Disassembly Chromosomal Proteins, Non-Histone / genetics Gene Expression Regulation, Neoplastic Genomic Instability Humans Male Mice Mice, Inbred BALB C Pancreatic Neoplasms / genetics Receptors, Cell Surface / metabolism Up-Regulation Vacuolar Proton-Translocating ATPases / metabolism Whole Genome Sequencing

Journal

Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179

Informations de publication

Date de publication:
27 11 2020
Historique:
received: 16 11 2018
accepted: 23 10 2020
entrez: 28 11 2020
pubmed: 29 11 2020
medline: 24 6 2021
Statut: epublish

Résumé

(Pro)renin receptor [(P)RR] has a role in various diseases, such as cardiovascular and renal disorders and cancer. Aberrant (P)RR expression is prevalent in pancreatic ductal adenocarcinoma (PDAC) which is the most common pancreatic cancer. Here we show whether aberrant expression of (P)RR directly leads to genomic instability in human pancreatic ductal epithelial (HPDE) cells. (P)RR-expressing HPDE cells show obvious cellular atypia. Whole genome sequencing reveals that aberrant (P)RR expression induces large numbers of point mutations and structural variations at the genome level. A (P)RR-expressing cell population exhibits tumour-forming ability, showing both atypical nuclei characterised by distinctive nuclear bodies and chromosomal abnormalities. (P)RR overexpression upregulates SWItch/Sucrose Non-Fermentable (SWI/SNF)-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 5 (SMARCA5) through a direct molecular interaction, which results in the failure of several genomic stability pathways. These data reveal that aberrant (P)RR expression contributes to the early carcinogenesis of PDAC.

Identifiants

DOI: 10.1038/s42003-020-01434-x PMID: 33247206 PMC: PMC7695732
pubmed: 33247206
doi: 10.1038/s42003-020-01434-x
pii: 10.1038/s42003-020-01434-x
pmc: PMC7695732
doi:

Substances chimiques

ATP6AP2 protein, human 0
Chromosomal Proteins, Non-Histone 0
Receptors, Cell Surface 0
Adenosine Triphosphatases EC 3.6.1.-
SMARCA5 protein, human EC 3.6.1.-
Vacuolar Proton-Translocating ATPases EC 3.6.1.-

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

724

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Auteurs

Yuki Shibayama (Y)

Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, 761-0793, Japan.

Kazuo Takahashi (K)

Department of Nephrology, Fujita Health University School of Medicine, Aichi, 470-1192, Japan.

Hisateru Yamaguchi (H)

Division of Biomedical Polymer Science, Institute for Comprehensive Medical Science, Fujita Health University School of Medicine, Aichi, 470-1192, Japan.
Department of Medical Technology, School of Nursing and Medical Care, Yokkaichi Nursing and Medical Care University, Mie, 512-8045, Japan.
ORCID: 0000-0002-4507-9598

Jun Yasuda (J)

Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Miyagi, 980-8573, Japan.
Division of Molecular and Cellular Oncology, Miyagi Cancer Center Research Institute, Miyagi, 981-1293, Japan.

Daisuke Yamazaki (D)

Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, 761-0793, Japan.

Asadur Rahman (A)

Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, 761-0793, Japan.
ORCID: 0000-0002-9172-5343

Takayuki Fujimori (T)

Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa, 761-0793, Japan.
Fujimori Clinic for Internal Medicine and Gastroenterology, Kagawa, 761-8075, Japan.

Yoshihide Fujisawa (Y)

Health Science Research Center, Faculty of Medicine, Kagawa University, Kagawa, 761-0793, Japan.

Shinji Takai (S)

Department of Innovative Medicine, Graduate School of Medicine, Osaka Medical College, Osaka, 569-8686, Japan.

Toru Furukawa (T)

Department of Investigative Pathology, Tohoku University Graduate School of Medicine, Miyagi, 980-8575, Japan.
ORCID: 0000-0002-1083-2324

Tsutomu Nakagawa (T)

Department of Applied Life Science, Faculty of Applied Biological Sciences, Gifu University, Gifu, 501-1193, Japan.

Hiroyuki Ohsaki (H)

Department of Medical Biophysics, Kobe University Graduate School of Health Sciences, Hyogo, 654-0142, Japan.

Hideki Kobara (H)

Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa, 761-0793, Japan.

Jing Hao Wong (JH)

Department of Human Genetics, The University of Tokyo, Graduate School of Medicine, Tokyo, 113-0033, Japan.

Tsutomu Masaki (T)

Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa, 761-0793, Japan.

Yukio Yuzawa (Y)

Department of Nephrology, Fujita Health University School of Medicine, Aichi, 470-1192, Japan.

Hideyasu Kiyomoto (H)

Community Medical Support, Tohoku Medical Megabank Organization, Tohoku University, Miyagi, 980-8573, Japan.

Shinichi Yachida (S)

Department of Cancer Genome Informatics, Faculty of Medicine, Graduate School of Medicine, Osaka University, Osaka, 565-0871, Japan.

Akihiro Fujimoto (A)

Department of Human Genetics, The University of Tokyo, Graduate School of Medicine, Tokyo, 113-0033, Japan. afujimoto@m.u-tokyo.ac.jp.

Akira Nishiyama (A)

Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, 761-0793, Japan. akira@med.kagawa-u.ac.jp.
ORCID: 0000-0001-5971-820X

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Classifications MeSH

questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Acid anhydride hydrolases › Adenosine triphosphatases › Aberrant (pro)renin receptor expression...
questionsmedicales.fr › Eucaryotes › Animaux › Aberrant (pro)renin receptor expression...
questionsmedicales.fr › Maladies endocriniennes › Tumeurs des glandes endocrines › Tumeurs du pancréas › Carcinome du canal pancréatique › Aberrant (pro)renin receptor expression...
questionsmedicales.fr › Cellules › Cellules cultivées › Lignée cellulaire › Aberrant (pro)renin receptor expression...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Processus néoplasiques › Carcinogenèse › Transformation cellulaire néoplasique › Aberrant (pro)renin receptor expression...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Assemblage et désassemblage de la chromatine › Aberrant (pro)renin receptor expression...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Nucléoprotéines › Protéines chromosomiques nonhistones › Aberrant (pro)renin receptor expression...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes tumoraux › Aberrant (pro)renin receptor expression...
questionsmedicales.fr › Phénomènes génétiques › Instabilité du génome › Aberrant (pro)renin receptor expression...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Aberrant (pro)renin receptor expression...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Aberrant (pro)renin receptor expression...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée BALB C › Aberrant (pro)renin receptor expression...
questionsmedicales.fr › Maladies endocriniennes › Tumeurs des glandes endocrines › Tumeurs du pancréas › Aberrant (pro)renin receptor expression...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Aberrant (pro)renin receptor expression...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Régulation positive › Aberrant (pro)renin receptor expression...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › Pompes ioniques › Transporteurs de cations › Pompes à protons › Proton-Translocating ATPases › Vacuolar Proton-Translocating ATPases › Aberrant (pro)renin receptor expression...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Analyse de séquence d'ADN › Séquençage du génome entier › Aberrant (pro)renin receptor expression...