YAP1-mediated pancreatic stellate cell activation inhibits pancreatic cancer cell proliferation.

Adaptor Proteins, Signal Transducing / genetics Apoptosis Biomarkers, Tumor / genetics Cancer-Associated Fibroblasts / metabolism Carcinoma, Pancreatic Ductal / genetics Cell Proliferation Cells, Cultured Coculture Techniques Female Gene Expression Regulation, Neoplastic Humans Lymphatic Metastasis Male Middle Aged Osteonectin / genetics Pancreatic Neoplasms / genetics Pancreatic Stellate Cells / metabolism Paracrine Communication Prognosis Survival Rate Transcription Factors / genetics Tumor Microenvironment YAP-Signaling Proteins
Extracellular matrix Pancreatic ductal adenocarcinoma Pancreatic stellate cells Secreted protein acidic and cysteine rich Yes-associated protein 1

Journal

Cancer letters
ISSN: 1872-7980
Titre abrégé: Cancer Lett
Pays: Ireland
ID NLM: 7600053

Informations de publication

Date de publication:
10 Oct 2019
Historique:
received: 12 05 2019
revised: 09 07 2019
accepted: 20 07 2019
pubmed: 29 7 2019
medline: 22 5 2020
entrez: 29 7 2019
Statut: ppublish

Résumé

Pancreatic stellate cells (PSCs) are activated in pancreatic ductal adenocarcinoma (PDAC) and are responsible for dense desmoplastic stroma. Yes-associated protein 1 (YAP1) can induce cancer-associated fibroblast activation in liver and breast tumors, but its effect on PSCs is unknown. In the present study, we determined that YAP1 was highly expressed in the nuclei of PDAC-derived activated PSCs. RNAi-mediated or pharmacological inhibition of YAP1 led to PSC deactivation. In addition, YAP1 stimulated the expression of secreted protein acidic and cysteine rich (SPARC) in PSCs, which was inhibited by RUNX1. SPARC secreted from PSCs inhibited pancreatic cancer cell (PCC) proliferation. High expression of nuclear YAP1 in tumor stroma was significantly correlated with SPARC expression and fibrosis degree in human PDAC tissues. Our study revealed a critical role for YAP1 in the regulation of PSC activation and paracrine signaling. Our findings provide insights into a novel rationale for targeting YAP1 to reprogram the PDAC microenvironment.

Identifiants

DOI: 10.1016/j.canlet.2019.07.015 PMID: 31352078
pubmed: 31352078
pii: S0304-3835(19)30411-2
doi: 10.1016/j.canlet.2019.07.015
pii:
doi:

Substances chimiques

Adaptor Proteins, Signal Transducing 0
Biomarkers, Tumor 0
Osteonectin 0
SPARC protein, human 0
Transcription Factors 0
YAP-Signaling Proteins 0
YAP1 protein, human 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

51-60

Informations de copyright

Copyright © 2019 Elsevier B.V. All rights reserved.

Auteurs

Ying Xiao (Y)

Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, PR China; Molecular Pathology Research Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, PR China; Department of Pathology, Beijing Tsinghua Changgung Hospital, School of Clinic Medicine, Tsinghua University, Beijing, PR China.

Hui Zhang (H)

Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, PR China; Molecular Pathology Research Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, PR China.

Qiang Ma (Q)

Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, PR China; Molecular Pathology Research Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, PR China.

Rui Huang (R)

Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, PR China; Molecular Pathology Research Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, PR China.

Junliang Lu (J)

Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, PR China; Molecular Pathology Research Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, PR China.

Xiaolong Liang (X)

Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, PR China; Molecular Pathology Research Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, PR China.

Xuguang Liu (X)

Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, PR China; Molecular Pathology Research Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, PR China.

Zhiwen Zhang (Z)

Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, PR China; Molecular Pathology Research Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, PR China.

Lianyuan Yu (L)

Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, PR China; Molecular Pathology Research Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, PR China.

Junyi Pang (J)

Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, PR China; Molecular Pathology Research Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, PR China.

Liangrui Zhou (L)

Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, PR China; Molecular Pathology Research Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, PR China.

Tonghua Liu (T)

Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, PR China; Molecular Pathology Research Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, PR China. Electronic address: liuth_pumch192911@yahoo.com.

Huanwen Wu (H)

Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, PR China; Molecular Pathology Research Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, PR China. Electronic address: whw14093@163.com.

Zhiyong Liang (Z)

Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, PR China; Molecular Pathology Research Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, PR China. Electronic address: liangzhiyong1220@yahoo.com.

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protéines adaptatrices de la transduction du signal › YAP1-mediated pancreatic stellate cell...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Mort cellulaire › Mort cellulaire régulée › Apoptose › YAP1-mediated pancreatic stellate cell...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Marqueurs biologiques tumoraux › YAP1-mediated pancreatic stellate cell...
questionsmedicales.fr › Cellules › Cellules du tissu conjonctif › Fibroblastes › Fibroblastes associés au cancer › YAP1-mediated pancreatic stellate cell...
questionsmedicales.fr › Maladies endocriniennes › Tumeurs des glandes endocrines › Tumeurs du pancréas › Carcinome du canal pancréatique › YAP1-mediated pancreatic stellate cell...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Croissance › Processus de croissance cellulaire › Prolifération cellulaire › YAP1-mediated pancreatic stellate cell...
questionsmedicales.fr › Cellules › Cellules cultivées › YAP1-mediated pancreatic stellate cell...
questionsmedicales.fr › Techniques d'investigation › Techniques in vitro › Techniques de culture › Techniques de coculture › YAP1-mediated pancreatic stellate cell...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes tumoraux › YAP1-mediated pancreatic stellate cell...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › YAP1-mediated pancreatic stellate cell...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Processus néoplasiques › Métastase tumorale › Métastase lymphatique › YAP1-mediated pancreatic stellate cell...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › YAP1-mediated pancreatic stellate cell...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Glycoprotéines › Ostéonectine › YAP1-mediated pancreatic stellate cell...
questionsmedicales.fr › Maladies endocriniennes › Tumeurs des glandes endocrines › Tumeurs du pancréas › YAP1-mediated pancreatic stellate cell...
questionsmedicales.fr › Cellules › Cellules stellaires pancréatiques › YAP1-mediated pancreatic stellate cell...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Communication cellulaire › Communication paracrine › YAP1-mediated pancreatic stellate cell...
questionsmedicales.fr › Diagnostic › Pronostic › YAP1-mediated pancreatic stellate cell...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Collecte de données › Registre civil › Mortalité › Taux de survie › YAP1-mediated pancreatic stellate cell...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › YAP1-mediated pancreatic stellate cell...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Microenvironnement cellulaire › Microenvironnement tumoral › YAP1-mediated pancreatic stellate cell...
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 › YAP1-mediated pancreatic stellate cell...