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University","award":["22H03540"],"award-info":[{"award-number":["22H03540"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>The incidence of oral cancer has recently been increasing worldwide, particularly among young individuals and women. The primary risk factors for head and neck cancers, including oral and pharyngeal cancers, are smoking, alcohol consumption, poor oral hygiene, and repeated exposure to mechanical stimuli. However, approximately one-third of the patients with oral and pharyngeal cancers are neither smokers nor drinkers, which points to the existence of other mechanisms. Recently, human microbes have been linked to various diseases, including cancer. Oral pathogens, especially periodontal pathobionts, are reported to play a role in the development of colon and other types of cancer. In this study, we employed a series of bioinformatics analyses to pinpoint Fusobacterium nucleatum as the predominant oral bacterial species in oral and pharyngeal cancer tissue samples. We successfully isolated Fn. polymorphum from the saliva of patients with oral cancer and demonstrated that Fn. polymorphum indeed promoted oral squamous cell carcinoma development by activating YAP in a mouse tongue cancer model. Our research offers scientific evidence for the role of the oral microbiome in oral cancer progression and provides insights that would help in devising preventative strategies against oral cancer, potentially by altering oral bacterial profiles.<\/jats:p>","DOI":"10.3390\/microorganisms11122957","type":"journal-article","created":{"date-parts":[[2023,12,11]],"date-time":"2023-12-11T06:56:00Z","timestamp":1702277760000},"page":"2957","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Oral Microbial Profile Analysis in Patients with Oral and Pharyngeal Cancer Reveals That Tumoral Fusobacterium nucleatum Promotes Oral Cancer Progression by Activating YAP"],"prefix":"10.3390","volume":"11","author":[{"given":"Yuki","family":"Yamamoto","sequence":"first","affiliation":[{"name":"Department of Otolaryngology and Head & Neck Surgery, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan"},{"name":"Department of Otolaryngology and Head & Neck Surgery, Graduate School of Medicine, Osaka City University, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomonori","family":"Kamiya","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megumu","family":"Yano","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vu Thuong","family":"Huyen","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Oishi","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology and Head & Neck Surgery, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miki","family":"Nishio","sequence":"additional","affiliation":[{"name":"Division of Molecular and Cellular Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Division of Molecular and Cellular Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kishiko","family":"Sunami","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology and Head & Neck Surgery, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan"},{"name":"Department of Otolaryngology and Head & Neck Surgery, Graduate School of Medicine, Osaka City University, Osaka 545-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8934-0797","authenticated-orcid":false,"given":"Naoko","family":"Ohtani","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan"},{"name":"AMED-CREST, Japan Agency for Medical Research and Development (AMED), Tokyo 100-0004, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1219111","DOI":"10.3389\/fonc.2023.1219111","article-title":"Head and neck cancers survival in Europe, Taiwan, and Japan: Results from RARECAREnet Asia based on a privacy-preserving federated infrastructure","volume":"13","author":"Botta","year":"2023","journal-title":"Front. Oncol."},{"key":"ref_3","first-page":"7","article-title":"Oral health risks of tobacco use and effects of cessation","volume":"60","author":"Warnakulasuriya","year":"2010","journal-title":"Int. Dent. J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"214","DOI":"10.3389\/fimmu.2015.00214","article-title":"Chemokine function in periodontal disease and oral cavity cancer","volume":"6","author":"Sahingur","year":"2015","journal-title":"Front. 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Community Dent."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.biopha.2016.09.082","article-title":"Role of oral microbiome on oral cancers, a review","volume":"84","author":"Gholizadeh","year":"2016","journal-title":"Biomed. Pharmacother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1264\/jsme2.ME18113","article-title":"Spatial distribution and chemical tolerance of Streptococcus mutans within dual-species cariogenic biofilms","volume":"33","author":"Nakanishi","year":"2018","journal-title":"Microbes Environ."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1038\/nrmicro2381","article-title":"Oral multispecies biofilm development and the key role of cell-cell distance","volume":"8","author":"Kolenbrander","year":"2010","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/nrmicro2337","article-title":"Periodontitis: A polymicrobial disruption of host homeostasis","volume":"8","author":"Darveau","year":"2010","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1097\/CCO.0000000000000947","article-title":"Oral microbiome as a new research-target for supportive care and precision oncology","volume":"35","author":"Bruno","year":"2023","journal-title":"Curr. Opin. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1016\/j.biopha.2017.02.102","article-title":"Carcinogenesis mechanisms of Fusobacterium nucleatum","volume":"89","author":"Gholizadeh","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"6170","DOI":"10.1158\/1078-0432.CCR-19-0318","article-title":"Intratumoral Fusobacterium nucleatum levels predict therapeutic response to neoadjuvant chemotherapy in esophageal squamous cell carcinoma","volume":"25","author":"Yamamura","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2176","DOI":"10.1111\/1751-7915.13900","article-title":"A newly developed PCR-based method revealed distinct Fusobacterium nucleatum subspecies infection patterns in colorectal cancer","volume":"14","author":"Bi","year":"2021","journal-title":"Microb. Biotechnol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"eaay3324","DOI":"10.1126\/sciadv.aay3324","article-title":"YAP1 is a potent driver of the onset and progression of oral squamous cell carcinoma","volume":"6","author":"Omori","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.1002\/hed.25138","article-title":"Systematic review evaluating randomized controlled trials of smoking and alcohol cessation interventions in people with head and neck cancer and oral dysplasia","volume":"40","author":"Shingler","year":"2018","journal-title":"Head Neck"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1093\/carcin\/bgaa062","article-title":"Oral microbial dysbiosis and its performance in predicting oral cancer","volume":"42","author":"Su","year":"2021","journal-title":"Carcinogenesis"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/s00203-020-02011-w","article-title":"Dysbiosis of salivary microbiome and cytokines influence oral squamous cell carcinoma through inflammation","volume":"203","author":"Rai","year":"2021","journal-title":"Arch. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Pignatelli, P., Nuccio, F., Piattelli, A., and Curia, M.C. (2023). The role of Fusobacterium nucleatum in oral and colorectal carcinogenesis. Microorganisms, 11.","DOI":"10.3390\/microorganisms11092358"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5574","DOI":"10.1158\/1078-0432.CCR-16-1786","article-title":"Human microbiome Fusobacterium nucleatum in esophageal cancer tissue is associated with prognosis","volume":"22","author":"Yamamura","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1038\/s41598-017-02079-3","article-title":"Inflammatory bacteriome featuring Fusobacterium nucleatum and Pseudomonas aeruginosa identified in association with oral squamous cell carcinoma","volume":"7","author":"Nasher","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/S1368-8375(98)80012-2","article-title":"The microflora associated with human oral carcinomas","volume":"34","author":"Nagy","year":"1998","journal-title":"Oral Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1002\/ijc.32871","article-title":"Global trends in oral and pharyngeal cancer incidence and mortality","volume":"147","author":"Bosetti","year":"2020","journal-title":"Int. J. Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1126\/science.aaw2367","article-title":"The gut microbiota and colon cancer","volume":"364","author":"Garrett","year":"2019","journal-title":"Science"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.immuni.2015.01.010","article-title":"Binding of the Fap2 protein of Fusobacterium nucleatum to human inhibitory receptor TIGIT protects tumors from immune cell attack","volume":"42","author":"Gur","year":"2015","journal-title":"Immunity"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Pratap Singh, R., Kumari, N., Gupta, S., Jaiswal, R., Mehrotra, D., Singh, S., Mukherjee, S., and Kumar, R. (2023). Intratumoral microbiota changes with tumor stage and influences the immune signature of oral squamous cell carcinoma. Microbiol. Spectr., 11.","DOI":"10.1128\/spectrum.04596-22"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1111\/cas.14725","article-title":"The role of Hippo-YAP signaling in squamous cell carcinomas","volume":"112","author":"Maehama","year":"2021","journal-title":"Cancer Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1987780","DOI":"10.1080\/19490976.2021.1987780","article-title":"Fusobacterium nucleatum drives a pro-inflammatory intestinal microenvironment through metabolite receptor-dependent modulation of IL-17 expression","volume":"13","author":"Brennan","year":"2021","journal-title":"Gut Microbes"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1038\/nature12721","article-title":"Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells","volume":"504","author":"Furusawa","year":"2013","journal-title":"Nature"}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/11\/12\/2957\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:36:21Z","timestamp":1760132181000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/11\/12\/2957"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,10]]},"references-count":30,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["microorganisms11122957"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms11122957","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,10]]}}}