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The mechanisms leading to kidney tumor development remain uncharacterized and effective therapies are yet to be identified. Hence, the need to model these diseases in an experimental animal system (\n                    <jats:xref ref-type=\"bibr\">Kauffman et al., 2014<\/jats:xref>\n                    ). Here, we show that kidney-specific\n                    <jats:italic>TFEB<\/jats:italic>\n                    overexpression in transgenic mice, resulted in renal clear cells, multi-layered basement membranes, severe cystic pathology, and ultimately papillary carcinomas with hepatic metastases. These features closely recapitulate those observed in both\n                    <jats:italic>TFEB-<\/jats:italic>\n                    and\n                    <jats:italic>TFE3<\/jats:italic>\n                    -mediated human kidney tumors. Analysis of kidney samples revealed transcriptional induction and enhanced signaling of the WNT \u03b2-catenin pathway. WNT signaling inhibitors normalized the proliferation rate of primary kidney cells and significantly rescued the disease phenotype in vivo. These data shed new light on the mechanisms underlying\n                    <jats:italic>TFE-<\/jats:italic>\n                    fusion\n                    <jats:italic>RCCs<\/jats:italic>\n                    and suggest a possible therapeutic strategy based on the inhibition of the WNT pathway.\n                  <\/jats:p>","DOI":"10.7554\/elife.17047","type":"journal-article","created":{"date-parts":[[2016,9,23]],"date-time":"2016-09-23T10:01:05Z","timestamp":1474624865000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.17047","source":"Crossref","is-referenced-by-count":95,"title":["Modelling TFE renal cell carcinoma in mice reveals a critical role of WNT signaling"],"prefix":"10.7554","volume":"5","author":[{"given":"Alessia","family":"Calcagn\u00ec","sequence":"first","affiliation":[{"name":"Telethon Institute of Genetics and Medicine, TIGEM, Pozzuoli, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lotte","family":"kors","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine, TIGEM, Pozzuoli, Naples, Italy"},{"name":"Department of Pathology, Academical Medical Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Verschuren","sequence":"additional","affiliation":[{"name":"Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands"},{"name":"Department of Human Genetics, Leiden University Medical Center, Leiden, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossella","family":"De Cegli","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine, TIGEM, Pozzuoli, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolina","family":"Zampelli","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine, TIGEM, Pozzuoli, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edoardo","family":"Nusco","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine, TIGEM, Pozzuoli, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Confalonieri","sequence":"additional","affiliation":[{"name":"Molecular Medicine Program, European Institute of Oncology, Milan, Italy"},{"name":"IFOM, The FIRC Institute for Molecular Oncology Foundation, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Bertalot","sequence":"additional","affiliation":[{"name":"Molecular Medicine Program, European Institute of Oncology, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Pece","sequence":"additional","affiliation":[{"name":"Molecular Medicine Program, European Institute of Oncology, Milan, Italy"},{"name":"Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmine","family":"Settembre","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine, TIGEM, Pozzuoli, Naples, Italy"},{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States"},{"name":"Jan and Dan Duncan Neurological Research Institute, Texas Children Hospital, Houston, United States"},{"name":"Medical Genetics, Federico II University, Naples, Italy"},{"name":"Medical Genetics, Department of Medical and Translational Sciences, Federico II University, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel G","family":"Malouf","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Groupe Hospitalier Pitie-Salpetriere, University Paris 6, Paris, France"},{"name":"Assistance Publique Hopitaux de Paris, University Paris 6, Paris, France"},{"name":"Faculty of Medicine Pierre et Marie Curie, University Paris 6, Paris, France"},{"name":"Institut Universitaire de Cancerologie GRC5, University Paris 6, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaklien C","family":"Leemans","sequence":"additional","affiliation":[{"name":"Department of Pathology, Academical Medical Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emile","family":"de Heer","sequence":"additional","affiliation":[{"name":"Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Salvatore","sequence":"additional","affiliation":[{"name":"IRCCS-SDN, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorien JM","family":"Peters","sequence":"additional","affiliation":[{"name":"Department of 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