{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T22:16:40Z","timestamp":1770761800305,"version":"3.50.0"},"reference-count":42,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,6,18]],"date-time":"2015-06-18T00:00:00Z","timestamp":1434585600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:sec><jats:label\/><jats:p>Cavin\u20102 (CVN2) affects formation of large caveolae, which are membrane\u2010rich cholesterol domains associated with several functions in signal transduction. Accumulating evidence suggests that CVN2 is present in many cellular types; however, the molecular mechanisms of CVN2 in cancers and its clinical relevance are unknown. We proposed a mechanism by which CVN2 regulates caveolin\u20101 expression leading to slow cellular proliferation by inactivation of the extracellular regulated kinase (ERK) pathway. Quantitative reverse transcriptase\u2010polymerase chain reaction and immunoblot analyses were used to assess the CVN2 regulation mechanism in oral squamous cell carcinoma (OSCC). Immunohistochemistry (IHC) was performed to analyze the correlation between CVN2 expression and clinical behavior in 115 patients with OSCC. A CVN2 overexpressed model of OSCC cells (oeCVN2 cells) was used for functional experiments. CVN2 expression was down\u2010regulated significantly (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05) in OSCCs compared with normal counterparts in vitro and in vivo. In addition to the findings that a serum deprivation culture induced up\u2010regulation of CVN2 and slowed cellular proliferation, oeCVN2 cell growth decreased because of cell\u2010cycle arrest at the G1 phase resulting from up\u2010regulated cyclin\u2010dependent kinase inhibitors (p21<jats:sup>Cip1<\/jats:sup> and p27<jats:sup>Kip1<\/jats:sup>) and down\u2010regulated cyclins (cyclin D1, cyclin E) and cyclin\u2010dependent kinases (CDK2, CDK4, and CDK6). Interestingly, CVN2 overexpression facilitated caveolin\u20101 recruitment and colocalization with each other. We also found decreased ERK phosphorylation levels, an upstream event in cell\u2010cycle arrest. Clinically, IHC data from primary OSCCs showed high tumoral progression in CVN2\u2010negative patients with OSCC. CVN2 may be a possible key regulator of OSCC progression via the CVN2\/caveolin\u20101\/ERK pathway and a potential therapeutic target for developing new treatments for OSCCs. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mc.22347","type":"journal-article","created":{"date-parts":[[2015,6,18]],"date-time":"2015-06-18T15:43:08Z","timestamp":1434642188000},"page":"1037-1047","source":"Crossref","is-referenced-by-count":9,"title":["Cavin\u20102 in oral cancer: A potential predictor for tumor progression"],"prefix":"10.1002","volume":"55","author":[{"given":"Motoharu","family":"Unozawa","sequence":"first","affiliation":[{"name":"Department of Oral Science Graduate School of Medicine Chiba University Chuo\u2010ku Chiba Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsushi","family":"Kasamatsu","sequence":"additional","affiliation":[{"name":"Department of Dentistry and Oral\u2010Maxillofacial Surgery Chiba University Hospital Chuo\u2010ku 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