{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T06:02:11Z","timestamp":1784613731219,"version":"3.55.0"},"reference-count":75,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2017,7,11]],"date-time":"2017-07-11T00:00:00Z","timestamp":1499731200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"},{"start":{"date-parts":[[2017,7,11]],"date-time":"2017-07-11T00:00:00Z","timestamp":1499731200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"},{"start":{"date-parts":[[2017,7,11]],"date-time":"2017-07-11T00:00:00Z","timestamp":1499731200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["NIH R01,AR062080"],"award-info":[{"award-number":["NIH R01,AR062080"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    Increased mTORC1 signaling from\n                    <jats:italic>TSC1\/TSC2<\/jats:italic>\n                    inactivation is found in cancer and causes tuberous sclerosis complex (TSC). The role of mesenchymal-derived cells in TSC tumorigenesis was investigated through disruption of\n                    <jats:italic>Tsc2<\/jats:italic>\n                    in craniofacial and limb bud mesenchymal progenitors. Tsc2cKO\n                    <jats:sup>Prrx1-cre<\/jats:sup>\n                    mice had shortened lifespans and extensive hamartomas containing abnormal tortuous, dilated vessels prominent in the forelimbs. Abnormalities were blocked by the mTORC1 inhibitor sirolimus. A Tsc2\/mTORC1 expression signature identified in Tsc2-deficient fibroblasts was also increased in bladder cancers with\n                    <jats:italic>TSC1<\/jats:italic>\n                    \/\n                    <jats:italic>TSC2<\/jats:italic>\n                    mutations in the TCGA database. Signature component\n                    <jats:italic>Lgals3<\/jats:italic>\n                    encoding galectin-3 was increased in Tsc2-deficient cells and serum of Tsc2cKO\n                    <jats:sup>Prrx1<\/jats:sup>\n                    -cre mice. Galectin-3 was increased in TSC-related skin tumors, angiomyolipomas, and lymphangioleiomyomatosis with serum levels in patients with lymphangioleiomyomatosis correlating with impaired lung function and angiomyolipoma presence. Our results demonstrate Tsc2-deficient mesenchymal progenitors cause aberrant morphogenic signals, and identify an expression signature including\n                    <jats:italic>Lgals3<\/jats:italic>\n                    relevant for human disease of\n                    <jats:italic>TSC1\/TSC2<\/jats:italic>\n                    inactivation and mTORC1 hyperactivity.\n                  <\/jats:p>","DOI":"10.7554\/elife.23202","type":"journal-article","created":{"date-parts":[[2017,7,11]],"date-time":"2017-07-11T05:00:53Z","timestamp":1499749253000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.23202","source":"Crossref","is-referenced-by-count":18,"title":["Tsc2 disruption in mesenchymal progenitors results in tumors with vascular anomalies overexpressing Lgals3"],"prefix":"10.7554","volume":"6","author":[{"given":"Peter J","family":"Klover","sequence":"first","affiliation":[{"name":"Department of Dermatology, Uniformed Services University of the Health Sciences, Bethesda, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajesh L","family":"Thangapazham","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Uniformed Services University of the Health Sciences, Bethesda, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiro","family":"Kato","sequence":"additional","affiliation":[{"name":"Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-an","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Uniformed Services University of the Health Sciences, Bethesda, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stasia A","family":"Anderson","sequence":"additional","affiliation":[{"name":"Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Diagnostic and Research Services Branch, National Institutes of Health, Bethesda, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy K","family":"Steagall","sequence":"additional","affiliation":[{"name":"Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaowei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Uniformed Services University of the Health Sciences, Bethesda, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"McCart","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Uniformed Services University of the Health Sciences, Bethesda, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neera","family":"Nathan","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Uniformed Services University of the Health Sciences, Bethesda, United States"},{"name":"Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua D","family":"Bernstock","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Uniformed Services University of the Health Sciences, Bethesda, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew D","family":"Wilkerson","sequence":"additional","affiliation":[{"name":"Department of Anatomy Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, United States"},{"name":"The American Genome Center, Uniformed Services University of the Health Sciences, Bethesda, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clifton L","family":"Dalgard","sequence":"additional","affiliation":[{"name":"Department of Anatomy Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, United States"},{"name":"The American Genome Center, Uniformed Services University of the Health Sciences, Bethesda, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Moss","sequence":"additional","affiliation":[{"name":"Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5161-1974","authenticated-orcid":true,"given":"Thomas N","family":"Darling","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Uniformed 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