{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T04:21:00Z","timestamp":1790396460532,"version":"4.1.0"},"reference-count":89,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,10]],"date-time":"2023-01-10T00:00:00Z","timestamp":1673308800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institute of Health","doi-asserted-by":"publisher","award":["DE028480"],"award-info":[{"award-number":["DE028480"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institute of Health","doi-asserted-by":"publisher","award":["DE023526"],"award-info":[{"award-number":["DE023526"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity and is linked to tobacco exposure, alcohol consumption, and human papillomavirus infection. Despite therapeutic advances, a lack of molecular understanding of disease etiology, and delayed diagnoses continue to negatively affect survival. The identification of oncogenic drivers and prognostic biomarkers by leveraging bulk and single-cell RNA-sequencing datasets of OSCC can lead to more targeted therapies and improved patient outcomes. However, the generation, analysis, and continued utilization of additional genetic and genomic tools are warranted. Tobacco-induced OSCC can be modeled in mice via 4-nitroquinoline 1-oxide (4NQO), which generates a spectrum of neoplastic lesions mimicking human OSCC and upregulates the oncogenic master transcription factor p63. Here, we molecularly characterized established mouse 4NQO treatment-derived OSCC cell lines and utilized RNA and chromatin immunoprecipitation-sequencing to uncover the global p63 gene regulatory and signaling network. We integrated our p63 datasets with published bulk and single-cell RNA-sequencing of mouse 4NQO-treated tongue and esophageal tumors, respectively, to generate a p63-driven gene signature that sheds new light on the role of p63 in murine OSCC. Our analyses reveal known and novel players, such as COTL1, that are regulated by p63 and influence various oncogenic processes, including metastasis. The identification of new sets of potential biomarkers and pathways, some of which are functionally conserved in human OSCC and can prognosticate patient survival, offers new avenues for future mechanistic studies.<\/jats:p>","DOI":"10.3390\/cancers15020446","type":"journal-article","created":{"date-parts":[[2023,1,11]],"date-time":"2023-01-11T03:40:35Z","timestamp":1673408435000},"page":"446","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A Systemic and Integrated Analysis of p63-Driven Regulatory Networks in Mouse Oral Squamous Cell Carcinoma"],"prefix":"10.3390","volume":"15","author":[{"given":"Alexandra Ruth","family":"Glathar","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0607-6631","authenticated-orcid":false,"given":"Akinsola","family":"Oyelakin","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kasturi Bala","family":"Nayak","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Sosa","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rose-Anne","family":"Romano","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, School of Dental Medicine, State University of New York at Buffalo, Buffalo, NY 14214, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9574-4576","authenticated-orcid":false,"given":"Satrajit","family":"Sinha","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14203, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/nrc2982","article-title":"The Molecular Biology of Head and Neck Cancer","volume":"11","author":"Leemans","year":"2011","journal-title":"Nat. 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