{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T14:10:33Z","timestamp":1779286233585,"version":"3.51.4"},"reference-count":188,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2019,3,26]],"date-time":"2019-03-26T00:00:00Z","timestamp":1553558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Head and neck squamous cell carcinoma (HNSCC) defines a group of solid tumors originating from the mucosa of the upper aerodigestive tract, pharynx, larynx, mouth, and nasal cavity. It has a metastatic evolution and poor prognosis and is the sixth most common cancer in the world, with 600,000 new cases reported every year. HNSCC heterogeneity and complexity is reflected in a multistep progression, involving crosstalk between several molecular pathways. The Notch pathway is associated with major events supporting cancerogenic evolution: cell proliferation, self-renewal, angiogenesis, and preservation of a pro-oncogenic microenvironment. Additionally, Notch is pivotal in tumor development and plays a dual role acting as both oncogene and tumor suppressor. In this review, we summarize the role of the Notch pathway in HNSCC, with a special focus on its compelling role in major events of tumor initiation and growth.<\/jats:p>","DOI":"10.3390\/ijms20061520","type":"journal-article","created":{"date-parts":[[2019,3,27]],"date-time":"2019-03-27T05:03:12Z","timestamp":1553662992000},"page":"1520","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Multifactorial Contribution of Notch Signaling in Head and Neck Squamous Cell Carcinoma"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0057-1757","authenticated-orcid":false,"given":"Cristina","family":"Porcheri","sequence":"first","affiliation":[{"name":"University of Zurich, Institute of Oral Biology, Plattenstrasse 11, CH-8032 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian Thomas","family":"Meisel","sequence":"additional","affiliation":[{"name":"University of Zurich, Institute of Oral Biology, Plattenstrasse 11, CH-8032 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9812-9982","authenticated-orcid":false,"given":"Thimios","family":"Mitsiadis","sequence":"additional","affiliation":[{"name":"University of Zurich, Institute of Oral Biology, Plattenstrasse 11, CH-8032 Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,3,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1136\/bmj.325.7368.822","article-title":"Squamous cell carcinomas of the head and neck","volume":"325","author":"Sanderson","year":"2002","journal-title":"BMJ"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1097\/00005537-200010000-00009","article-title":"More aggressive behavior of squamous cell carcinoma of the anterior tongue in young women","volume":"110","author":"Vargas","year":"2000","journal-title":"Laryngoscope"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1002\/hed.20145","article-title":"Impact of young age on prognosis for head and neck cancer: A matched-pair analysis","volume":"27","author":"Gilroy","year":"2005","journal-title":"Head Neck"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e57","DOI":"10.1016\/j.oraloncology.2009.01.011","article-title":"Age as a determinant of outcomes for patients with oral cancer","volume":"45","author":"Goldenberg","year":"2009","journal-title":"Oral Oncol."},{"key":"ref_5","first-page":"13","article-title":"Angiogenesis in oral squamous cell carcinoma","volume":"25","author":"Ascani","year":"2005","journal-title":"Acta Otorhinol. 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