RRC ID 37509
著者 Unozawa M, Kasamatsu A, Higo M, Fukumoto C, Koyama T, Sakazume T, Nakashima D, Ogawara K, Yokoe H, Shiiba M, Tanzawa H, Uzawa K.
タイトル Cavin-2 in oral cancer: A potential predictor for tumor progression.
ジャーナル Mol Carcinog
Abstract Cavin-2 (CVN2) affects formation of large caveolae, which are membrane-rich 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-1 expression leading to slow cellular proliferation by inactivation of the extracellular regulated kinase (ERK) pathway. Quantitative reverse transcriptase-polymerase 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-regulated significantly (P < 0.05) in OSCCs compared with normal counterparts in vitro and in vivo. In addition to the findings that a serum deprivation culture induced up-regulation of CVN2 and slowed cellular proliferation, oeCVN2 cell growth decreased because of cell-cycle arrest at the G1 phase resulting from up-regulated cyclin-dependent kinase inhibitors (p21(Cip1) and p27(Kip1) ) and down-regulated cyclins (cyclin D1, cyclin E) and cyclin-dependent kinases (CDK2, CDK4, and CDK6). Interestingly, CVN2 overexpression facilitated caveolin-1 recruitment and colocalization with each other. We also found decreased ERK phosphorylation levels, an upstream event in cell-cycle arrest. Clinically, IHC data from primary OSCCs showed high tumoral progression in CVN2-negative patients with OSCC. CVN2 may be a possible key regulator of OSCC progression via the CVN2/caveolin-1/ERK pathway and a potential therapeutic target for developing new treatments for OSCCs. © 2015 Wiley Periodicals, Inc.
巻・号 55(6)
ページ 1037-47
公開日 2016-6-1
DOI 10.1002/mc.22347
PMID 26086332
MeSH Carcinoma, Squamous Cell / genetics Carcinoma, Squamous Cell / metabolism Carcinoma, Squamous Cell / pathology* Carrier Proteins / genetics* Carrier Proteins / metabolism* Caveolin 1 / metabolism* Cell Cycle Cell Line, Tumor Cell Proliferation Disease Progression Down-Regulation Gene Expression Regulation, Neoplastic Humans MAP Kinase Signaling System Mouth Neoplasms / genetics Mouth Neoplasms / metabolism Mouth Neoplasms / pathology* Phosphate-Binding Proteins Phosphorylation
IF 3.825
引用数 11
WOS 分野 ONCOLOGY BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 HSC-3(RCB1975) HSC-2(RCB1945) HSC-4(RCB1902) SAS(RCB1974)