{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T14:23:23Z","timestamp":1790519003169,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,6,4]],"date-time":"2019-06-04T00:00:00Z","timestamp":1559606400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["IG21408"],"award-info":[{"award-number":["IG21408"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["GR\u20102011\u201002348356"],"award-info":[{"award-number":["GR\u20102011\u201002348356"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:p>\n                    Malignant pleural mesothelioma (MPM) is a tumor with high chemoresistance and poor prognosis. MPM\u2010initiating cells (ICs) are known to be drug resistant, but it is unknown if and how stemness\u2010related pathways determine chemoresistance. Moreover, there are no predictive markers of IC\u2010associated chemoresistance. Aim of this work is to clarify if and by which mechanisms the chemoresistant phenotype of MPM IC was due to specific stemness\u2010related pathways. We generated MPM IC from primary MPM samples and compared the gene expression and chemo\u2010sensitivity profile of IC and differentiated\/adherent cells (AC) of the same patient. Compared to AC, IC had upregulated the drug efflux transporter ABCB5 that determined resistance to cisplatin and pemetrexed.\n                    <jats:italic>ABCB5<\/jats:italic>\n                    \u2010knocked\u2010out (KO) IC clones were resensitized to the drugs\n                    <jats:italic>in vitro<\/jats:italic>\n                    and in patient\u2010derived xenografts. ABCB5 was transcriptionally activated by the Wnt\/GSK3\u03b2\/\u03b2\u2010catenin\/c\u2010myc axis that also increased IL\u20108 and IL\u20101\u03b2 production.\n                    <jats:italic>IL\u20108<\/jats:italic>\n                    and\n                    <jats:italic>IL\u20101\u03b2<\/jats:italic>\n                    \u2010KO IC clones reduced the c\u2010myc\u2010driven transcription of ABCB5 and reacquired chemosensitivity.\n                    <jats:italic>ABCB5<\/jats:italic>\n                    \u2010KO clones had lower IL\u20108 and IL\u20101\u03b2 secretion, and c\u2010myc transcriptional activity, suggesting that either Wnt\/GSK3\u03b2\/\u03b2\u2010catenin and IL\u20108\/IL\u20101\u03b2 signaling drive c\u2010myc\u2010mediated transcription of ABCB5. ABCB5 correlated with lower time\u2010to\u2010progression and overall survival in MPM patients treated with cisplatin and pemetrexed. Our work identified multiple autocrine loops linking stemness pathways and resistance to cisplatin and pemetrexed in MPM IC. ABCB5 may represent a new target to chemosensitize MPM IC and a potential biomarker to predict the response to the first\u2010line chemotherapy in MPM patients.\n                  <\/jats:p>","DOI":"10.1002\/ijc.32419","type":"journal-article","created":{"date-parts":[[2019,5,20]],"date-time":"2019-05-20T12:10:27Z","timestamp":1558354227000},"page":"192-207","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Wnt\/IL\u20101\u03b2\/IL\u20108 autocrine circuitries control chemoresistance in mesothelioma initiating cells by inducing ABCB5"],"prefix":"10.1002","volume":"146","author":[{"given":"Vladan","family":"Milosevic","sequence":"first","affiliation":[{"name":"Department of Oncology University of Torino  Torino Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Kopecka","sequence":"additional","affiliation":[{"name":"Department of Oncology University of Torino  Torino Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris C.","family":"Salaroglio","sequence":"additional","affiliation":[{"name":"Department of Oncology University of Torino  Torino Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Libener","sequence":"additional","affiliation":[{"name":"Pathology Division S. Antonio and Biagio Hospital  Alessandria Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Napoli","sequence":"additional","affiliation":[{"name":"Department of Oncology University of Torino  Torino Italy"},{"name":"Pathology Unit, Department of Oncology at San Luigi Hospital University of Torino  Orbassano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Izzo","sequence":"additional","affiliation":[{"name":"Department of Oncology University of Torino  Torino Italy"},{"name":"Pathology Unit, Department of Oncology at San Luigi Hospital University of Torino  Orbassano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Orecchia","sequence":"additional","affiliation":[{"name":"Pathology Division S. Antonio and Biagio Hospital  Alessandria Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Preeta","family":"Ananthanarayanan","sequence":"additional","affiliation":[{"name":"Department of Oncology University of Torino  Torino Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Bironzo","sequence":"additional","affiliation":[{"name":"Department of Oncology University of Torino  Torino Italy"},{"name":"Thoracic Oncology Unit and Medical Oncology Division, Department of Oncology at San Luigi Hospital  University of Torino  Orbassano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Grosso","sequence":"additional","affiliation":[{"name":"Oncology Division S. Antonio and Biagio Hospital  Alessandria Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Tabb\u00f2","sequence":"additional","affiliation":[{"name":"Department of Oncology University of Torino  Torino Italy"},{"name":"Thoracic Oncology Unit and Medical Oncology Division, Department of Oncology at San Luigi Hospital  University of Torino  Orbassano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Comunanza","sequence":"additional","affiliation":[{"name":"Department of Oncology University of Torino  Torino Italy"},{"name":"Candiolo Cancer Institute \u2010 FPO IRCCS  Candiolo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teodora","family":"Alexa\u2010Stratulat","sequence":"additional","affiliation":[{"name":"Department of Oncology University of Torino  Torino Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Bussolino","sequence":"additional","affiliation":[{"name":"Department of Oncology University of Torino  Torino Italy"},{"name":"Candiolo Cancer Institute \u2010 FPO IRCCS  Candiolo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisella","family":"Righi","sequence":"additional","affiliation":[{"name":"Department of Oncology University of Torino  Torino Italy"},{"name":"Pathology Unit, Department of Oncology at San Luigi Hospital University of Torino  Orbassano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Novello","sequence":"additional","affiliation":[{"name":"Department of Oncology University of Torino  Torino Italy"},{"name":"Thoracic Oncology Unit and Medical Oncology Division, Department of Oncology at San Luigi Hospital  University of Torino  Orbassano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio V.","family":"Scagliotti","sequence":"additional","affiliation":[{"name":"Department of Oncology University of Torino  Torino Italy"},{"name":"Thoracic Oncology Unit and Medical Oncology Division, Department of Oncology at San Luigi Hospital  University of Torino  Orbassano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9787-4836","authenticated-orcid":false,"given":"Chiara","family":"Riganti","sequence":"additional","affiliation":[{"name":"Department of Oncology University of Torino  Torino Italy"},{"name":"Interdepartmental Center \u201cG. 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