{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:59:14Z","timestamp":1787018354421,"version":"build-2736575974"},"reference-count":48,"publisher":"American Society for Clinical Investigation","issue":"11","license":[{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"vor","delay-in-days":53,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"crossref","award":["RO1DE024179"],"award-info":[{"award-number":["RO1DE024179"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Cancer Institute","award":["RO1CA235620"],"award-info":[{"award-number":["RO1CA235620"]}]},{"name":"National Cancer Institute","award":["U01DE025181"],"award-info":[{"award-number":["U01DE025181"]}]},{"DOI":"10.13039\/100004917","name":"Cancer Prevention and Research Institute of Texas","doi-asserted-by":"crossref","award":["RP200369"],"award-info":[{"award-number":["RP200369"]}],"id":[{"id":"10.13039\/100004917","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,8]]},"abstract":"<jats:p>\n                    Inactivating\n                    <jats:italic>NOTCH1<\/jats:italic>\n                    mutations in head and neck squamous cell carcinoma (HNSCC) were described over a decade ago, suggesting a tumor suppressor function \u2014 unlike its oncogenic role in other tumors. Today, much debate persists regarding a putative oncogenic role in HNSCC as well, with reports that NOTCH1 signaling drives tumor growth and a cancer stem cell (CSC) phenotype. In this work, comprehensive experiments unequivocally demonstrate that\n                    <jats:italic>NOTCH1<\/jats:italic>\n                    is a tumor suppressor in HNSCC regardless of mutation or activation status and that it reduces CSC frequency. We developed a signature of NOTCH1 activation showing the pathway is associated with very early differentiation, an altered tumor microenvironment, and better prognosis. Clarifying whether\n                    <jats:italic>NOTCH1<\/jats:italic>\n                    occasionally functions as an oncogenic driver in HNSCC is crucial to prognosis and personalized therapy. The results presented unify the field, reconcile conflicting data, and provide critical insights into the biological and clinical significance of\n                    <jats:italic>NOTCH1<\/jats:italic>\n                    , with broader implications in other squamous carcinomas with\n                    <jats:italic>NOTCH1<\/jats:italic>\n                    mutations.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.202414","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T16:00:13Z","timestamp":1776355213000},"source":"Crossref","is-referenced-by-count":1,"title":["NOTCH1 acts as a tumor suppressor that induces early differentiation in head and neck cancer"],"prefix":"10.1172","volume":"11","author":[{"given":"Chenfei","family":"Huang","sequence":"first","affiliation":[{"name":"Bobby R. Alford Department of Otolaryngology-Head and Neck Surgery, Baylor College of Medicine, Houston, Texas, USA."},{"name":"Celularity Inc., Florham Park, New Jersey, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shhyam","family":"Moorthy","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas, USA."},{"name":"Merck, Rahway, New Jersey, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuli","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas, USA."},{"name":"Department of Head and Neck, Sun Yat-sen University Cancer Center, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazi M.","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Bobby R. 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