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Loss of C/EBP-β LIP drives cisplatin resistance in malignant pleural mesothelioma.

Identifieur interne : 000109 ( PubMed/Corpus ); précédent : 000108; suivant : 000110

Loss of C/EBP-β LIP drives cisplatin resistance in malignant pleural mesothelioma.

Auteurs : Joanna Kopecka ; Iris C. Salaroglio ; Luisella Righi ; Roberta Libener ; Sara Orecchia ; Federica Grosso ; Vladan Milosevic ; Preeta Ananthanarayanan ; Luisa Ricci ; Enrica Capelletto ; Monica Pradotto ; Francesca Napoli ; Massimo Di Maio ; Silvia Novello ; Menachem Rubinstein ; Giorgio V. Scagliotti ; Chiara Riganti

Source :

RBID : pubmed:29748013

English descriptors

Abstract

Cisplatin-based chemotherapy is moderately active in malignant pleural mesothelioma (MPM) due to intrinsic drug resistance and to low immunogenicity of MPM cells. CAAT/enhancer binding protein (C/EBP)-β LIP is a pro-apoptotic and chemosensitizing transcription factor activated in response to endoplasmic reticulum (ER) stress.

DOI: 10.1016/j.lungcan.2018.03.022
PubMed: 29748013

Links to Exploration step

pubmed:29748013

Le document en format XML

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<name sortKey="Ricci, Luisa" sort="Ricci, Luisa" uniqKey="Ricci L" first="Luisa" last="Ricci">Luisa Ricci</name>
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<name sortKey="Pradotto, Monica" sort="Pradotto, Monica" uniqKey="Pradotto M" first="Monica" last="Pradotto">Monica Pradotto</name>
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<name sortKey="Scagliotti, Giorgio V" sort="Scagliotti, Giorgio V" uniqKey="Scagliotti G" first="Giorgio V" last="Scagliotti">Giorgio V. Scagliotti</name>
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<nlm:affiliation>Oncology Division, S. Antonio and Biagio Hospital, Spalto Marengo, 15121, Alessandria, Italy. Electronic address: fgrosso@ospedale.al.it.</nlm:affiliation>
</affiliation>
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<name sortKey="Milosevic, Vladan" sort="Milosevic, Vladan" uniqKey="Milosevic V" first="Vladan" last="Milosevic">Vladan Milosevic</name>
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<nlm:affiliation>Department of Oncology, University of Torino, via Santena 5/bis, 10126, Torino, Italy. Electronic address: vladan.milosevic@unito.it.</nlm:affiliation>
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<name sortKey="Ananthanarayanan, Preeta" sort="Ananthanarayanan, Preeta" uniqKey="Ananthanarayanan P" first="Preeta" last="Ananthanarayanan">Preeta Ananthanarayanan</name>
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<name sortKey="Ricci, Luisa" sort="Ricci, Luisa" uniqKey="Ricci L" first="Luisa" last="Ricci">Luisa Ricci</name>
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<nlm:affiliation>Department of Oncology, University of Torino, via Santena 5/bis, 10126, Torino, Italy. Electronic address: luisa.ricci@gmail.com.</nlm:affiliation>
</affiliation>
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<name sortKey="Capelletto, Enrica" sort="Capelletto, Enrica" uniqKey="Capelletto E" first="Enrica" last="Capelletto">Enrica Capelletto</name>
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<nlm:affiliation>Thoracic Unit and Medical Oncology Division, Department of Oncology at San Luigi Hospital, Regione Gonzole 10, University of Torino, Orbassano, Italy. Electronic address: enrica.capelletto@gmail.com.</nlm:affiliation>
</affiliation>
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<name sortKey="Pradotto, Monica" sort="Pradotto, Monica" uniqKey="Pradotto M" first="Monica" last="Pradotto">Monica Pradotto</name>
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<nlm:affiliation>Thoracic Unit and Medical Oncology Division, Department of Oncology at San Luigi Hospital, Regione Gonzole 10, University of Torino, Orbassano, Italy. Electronic address: monica.pradotto@unito.it.</nlm:affiliation>
</affiliation>
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<name sortKey="Napoli, Francesca" sort="Napoli, Francesca" uniqKey="Napoli F" first="Francesca" last="Napoli">Francesca Napoli</name>
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</affiliation>
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<name sortKey="Di Maio, Massimo" sort="Di Maio, Massimo" uniqKey="Di Maio M" first="Massimo" last="Di Maio">Massimo Di Maio</name>
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<nlm:affiliation>Medical Oncology Division, Department of Oncology at Mauriziano Hospital, Largo Filippo Turati 62, 10128, University of Torino, Italy. Electronic address: massimo.dimaio@unito.it.</nlm:affiliation>
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<name sortKey="Novello, Silvia" sort="Novello, Silvia" uniqKey="Novello S" first="Silvia" last="Novello">Silvia Novello</name>
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<nlm:affiliation>Thoracic Unit and Medical Oncology Division, Department of Oncology at San Luigi Hospital, Regione Gonzole 10, University of Torino, Orbassano, Italy. Electronic address: silvia.novello@unito.it.</nlm:affiliation>
</affiliation>
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<name sortKey="Rubinstein, Menachem" sort="Rubinstein, Menachem" uniqKey="Rubinstein M" first="Menachem" last="Rubinstein">Menachem Rubinstein</name>
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<nlm:affiliation>Department of Molecular Genetics, The Weizmann Institute of Science, Herzl Street 234, 76100, Rehovot, Israel. Electronic address: menachem.rubinstein@weizmann.ac.il.</nlm:affiliation>
</affiliation>
</author>
<author>
<name sortKey="Scagliotti, Giorgio V" sort="Scagliotti, Giorgio V" uniqKey="Scagliotti G" first="Giorgio V" last="Scagliotti">Giorgio V. Scagliotti</name>
<affiliation>
<nlm:affiliation>Thoracic Unit and Medical Oncology Division, Department of Oncology at San Luigi Hospital, Regione Gonzole 10, University of Torino, Orbassano, Italy. Electronic address: giorgio.scagliotti@unito.it.</nlm:affiliation>
</affiliation>
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<author>
<name sortKey="Riganti, Chiara" sort="Riganti, Chiara" uniqKey="Riganti C" first="Chiara" last="Riganti">Chiara Riganti</name>
<affiliation>
<nlm:affiliation>Department of Oncology, University of Torino, via Santena 5/bis, 10126, Torino, Italy. Electronic address: chiara.riganti@unito.it.</nlm:affiliation>
</affiliation>
</author>
</analytic>
<series>
<title level="j">Lung cancer (Amsterdam, Netherlands)</title>
<idno type="eISSN">1872-8332</idno>
<imprint>
<date when="2018" type="published">2018</date>
</imprint>
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<keywords scheme="KwdEn" xml:lang="en">
<term>Adaptor Proteins, Signal Transducing (genetics)</term>
<term>Adaptor Proteins, Signal Transducing (metabolism)</term>
<term>Antineoplastic Agents (therapeutic use)</term>
<term>Apoptosis</term>
<term>CCAAT-Enhancer-Binding Protein-beta (genetics)</term>
<term>CCAAT-Enhancer-Binding Protein-beta (metabolism)</term>
<term>CD8-Positive T-Lymphocytes (immunology)</term>
<term>Cisplatin (therapeutic use)</term>
<term>Dendritic Cells (immunology)</term>
<term>Drug Resistance, Neoplasm (genetics)</term>
<term>Humans</term>
<term>Lung Neoplasms (drug therapy)</term>
<term>Lung Neoplasms (genetics)</term>
<term>Lung Neoplasms (mortality)</term>
<term>Lymphocyte Activation</term>
<term>Mesothelioma (drug therapy)</term>
<term>Mesothelioma (genetics)</term>
<term>Mesothelioma (mortality)</term>
<term>Oligopeptides (pharmacology)</term>
<term>Pleural Neoplasms (drug therapy)</term>
<term>Pleural Neoplasms (mortality)</term>
<term>Prognosis</term>
<term>Proteolysis</term>
<term>Survival Analysis</term>
<term>Tumor Cells, Cultured</term>
<term>Ubiquitination</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en">
<term>Adaptor Proteins, Signal Transducing</term>
<term>CCAAT-Enhancer-Binding Protein-beta</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en">
<term>Adaptor Proteins, Signal Transducing</term>
<term>CCAAT-Enhancer-Binding Protein-beta</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en">
<term>Oligopeptides</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en">
<term>Antineoplastic Agents</term>
<term>Cisplatin</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en">
<term>Lung Neoplasms</term>
<term>Mesothelioma</term>
<term>Pleural Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en">
<term>Drug Resistance, Neoplasm</term>
<term>Lung Neoplasms</term>
<term>Mesothelioma</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en">
<term>CD8-Positive T-Lymphocytes</term>
<term>Dendritic Cells</term>
</keywords>
<keywords scheme="MESH" qualifier="mortality" xml:lang="en">
<term>Lung Neoplasms</term>
<term>Mesothelioma</term>
<term>Pleural Neoplasms</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Apoptosis</term>
<term>Humans</term>
<term>Lymphocyte Activation</term>
<term>Prognosis</term>
<term>Proteolysis</term>
<term>Survival Analysis</term>
<term>Tumor Cells, Cultured</term>
<term>Ubiquitination</term>
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<front>
<div type="abstract" xml:lang="en">Cisplatin-based chemotherapy is moderately active in malignant pleural mesothelioma (MPM) due to intrinsic drug resistance and to low immunogenicity of MPM cells. CAAT/enhancer binding protein (C/EBP)-β LIP is a pro-apoptotic and chemosensitizing transcription factor activated in response to endoplasmic reticulum (ER) stress.</div>
</front>
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<MedlineCitation Status="MEDLINE" Owner="NLM">
<PMID Version="1">29748013</PMID>
<DateCompleted>
<Year>2019</Year>
<Month>07</Month>
<Day>22</Day>
</DateCompleted>
<DateRevised>
<Year>2019</Year>
<Month>07</Month>
<Day>22</Day>
</DateRevised>
<Article PubModel="Print-Electronic">
<Journal>
<ISSN IssnType="Electronic">1872-8332</ISSN>
<JournalIssue CitedMedium="Internet">
<Volume>120</Volume>
<PubDate>
<Year>2018</Year>
<Month>06</Month>
</PubDate>
</JournalIssue>
<Title>Lung cancer (Amsterdam, Netherlands)</Title>
<ISOAbbreviation>Lung Cancer</ISOAbbreviation>
</Journal>
<ArticleTitle>Loss of C/EBP-β LIP drives cisplatin resistance in malignant pleural mesothelioma.</ArticleTitle>
<Pagination>
<MedlinePgn>34-45</MedlinePgn>
</Pagination>
<ELocationID EIdType="pii" ValidYN="Y">S0169-5002(18)30311-8</ELocationID>
<ELocationID EIdType="doi" ValidYN="Y">10.1016/j.lungcan.2018.03.022</ELocationID>
<Abstract>
<AbstractText Label="OBJECTIVES">Cisplatin-based chemotherapy is moderately active in malignant pleural mesothelioma (MPM) due to intrinsic drug resistance and to low immunogenicity of MPM cells. CAAT/enhancer binding protein (C/EBP)-β LIP is a pro-apoptotic and chemosensitizing transcription factor activated in response to endoplasmic reticulum (ER) stress.</AbstractText>
<AbstractText Label="MATERIALS AND METHODS">We investigated if LIP levels can predict the clinical response to cisplatin and survival of MPM patients receiving cisplatin-based chemotherapy. We studied the LIP-dependent mechanisms determining cisplatin-resistance and we identified pharmacological approaches targeting LIP, able to restore cisplatin sensitiveness, in patient-derived MPM cells and animal models. Results were analyzed by a one-way analysis of variance test.</AbstractText>
<AbstractText Label="RESULTS">We found that LIP was degraded by constitutive ubiquitination in primary MPM cells derived from patients poorly responsive to cisplatin. LIP ubiquitination was directly correlated with cisplatin chemosensitivity and was associated with patients' survival after chemotherapy. Overexpression of LIP restored cisplatin's pro-apoptotic effect by activating CHOP/TRB3/caspase 3 axis and up-regulating calreticulin, that triggered MPM cell phagocytosis by dendritic cells and expanded autologous anti-tumor CD8
<sup>+</sup>
CD107
<sup>+</sup>
T-cytotoxic lymphocytes. Proteasome inhibitor carfilzomib and lysosome inhibitor chloroquine prevented LIP degradation. The triple combination of carfilzomib, chloroquine and cisplatin increased ER stress-triggered apoptosis and immunogenic cell death in patients' samples, and reduced tumor growth in cisplatin-resistant MPM preclinical models.</AbstractText>
<AbstractText Label="CONCLUSION">The loss of LIP mediates cisplatin resistance, rendering LIP a possible predictor of cisplatin response in MPM patients. The association of proteasome and lysosome inhibitors reverses cisplatin resistance by restoring LIP levels and may represent a new adjuvant strategy in MPM treatment.</AbstractText>
<CopyrightInformation>Copyright © 2018 Elsevier B.V. All rights reserved.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y">
<Author ValidYN="Y">
<LastName>Kopecka</LastName>
<ForeName>Joanna</ForeName>
<Initials>J</Initials>
<AffiliationInfo>
<Affiliation>Department of Oncology, University of Torino, via Santena 5/bis, 10126, Torino, Italy. Electronic address: joanna.kopecka@unito.it.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Salaroglio</LastName>
<ForeName>Iris C</ForeName>
<Initials>IC</Initials>
<AffiliationInfo>
<Affiliation>Department of Oncology, University of Torino, via Santena 5/bis, 10126, Torino, Italy. Electronic address: irischiara.salaroglio@unito.it.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Righi</LastName>
<ForeName>Luisella</ForeName>
<Initials>L</Initials>
<AffiliationInfo>
<Affiliation>Pathology Unit, Department of Oncology at San Luigi Hospital, University of Torino, Regione Gonzole 10, 10043, Orbassano, Italy. Electronic address: luisella.righi@unito.it.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Libener</LastName>
<ForeName>Roberta</ForeName>
<Initials>R</Initials>
<AffiliationInfo>
<Affiliation>Pathology Division, S. Antonio and Biagio Hospital, Spalto Marengo, 15121, Alessandria, Italy. Electronic address: rlibener@ospedale.al.it.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Orecchia</LastName>
<ForeName>Sara</ForeName>
<Initials>S</Initials>
<AffiliationInfo>
<Affiliation>Pathology Division, S. Antonio and Biagio Hospital, Spalto Marengo, 15121, Alessandria, Italy. Electronic address: sorecchia@ospedale.al.it.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Grosso</LastName>
<ForeName>Federica</ForeName>
<Initials>F</Initials>
<AffiliationInfo>
<Affiliation>Oncology Division, S. Antonio and Biagio Hospital, Spalto Marengo, 15121, Alessandria, Italy. Electronic address: fgrosso@ospedale.al.it.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
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