{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T14:12:32Z","timestamp":1788531152661,"version":"build-2803163510"},"reference-count":92,"publisher":"American Society for Clinical Investigation","issue":"17","license":[{"start":{"date-parts":[[2022,9,8]],"date-time":"2022-09-08T00:00:00Z","timestamp":1662595200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Consortium for Canine Comparative Oncology","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]},{"DOI":"10.13039\/100008258","name":"Hyundai Hope On Wheels","doi-asserted-by":"crossref","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}],"id":[{"id":"10.13039\/100008258","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Duke Health Scholars Award","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,9,8]]},"abstract":"<jats:p>\n                    Osteosarcoma (OS) is a lethal disease with few known targeted therapies. Here, we show that decreased\n                    <jats:italic>ATRX<\/jats:italic>\n                    expression is associated with more aggressive tumor cell phenotypes, including increased growth, migration, invasion, and metastasis. These phenotypic changes correspond with activation of NF-\u03baB signaling, extracellular matrix remodeling, increased integrin \u03b1v\u03b23 expression, and ETS family transcription factor binding. Here, we characterize these changes in vitro, in vivo, and in a data set of human OS patients. This increased aggression substantially sensitizes\n                    <jats:italic>ATRX<\/jats:italic>\n                    -deficient OS cells to integrin signaling inhibition. Thus,\n                    <jats:italic>ATRX<\/jats:italic>\n                    plays an important tumor-suppression role in OS, and loss of function of this gene may underlie new therapeutic vulnerabilities. The relationship between\n                    <jats:italic>ATRX<\/jats:italic>\n                    expression and integrin binding, NF-\u03baB activation, and ETS family transcription factor binding has not been described in previous studies and may impact the pathophysiology of other diseases with\n                    <jats:italic>ATRX<\/jats:italic>\n                    loss, including other cancers and the ATR-X \u03b1 thalassemia intellectual disability syndrome.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.151583","type":"journal-article","created":{"date-parts":[[2022,9,7]],"date-time":"2022-09-07T14:01:03Z","timestamp":1662559263000},"source":"Crossref","is-referenced-by-count":27,"title":["Loss of ATRX promotes aggressive features of osteosarcoma with increased NF-\u03baB signaling and integrin binding"],"prefix":"10.1172","volume":"7","author":[{"given":"Suzanne","family":"Bartholf DeWitt","sequence":"first","affiliation":[{"name":"Department of Orthopaedic 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