Nuclear survivin promoted by acetylation is associated with the aggressive phenotype of oral squamous cell carcinoma
Nuclear survivin promoted by acetylation is associated with the aggressive phenotype of oral squamous cell carcinoma
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乙酰化促进的核生存素与口腔鳞状细胞癌的侵袭性表型相关。
DOI：
10.1080/15384101.2017.1310352
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发表时间：
2017-01-01
期刊：
影响因子：
4.3
通讯作者：
Deng, Jiong
中科院分区：
文献类型：
--
作者：
Liu, Shuli;Shi, Lei;Deng, Jiong
细胞凋亡途径的缺陷导致口腔癌的发生和进展。 Survivin 是凋亡蛋白抑制剂 (IAP) 家族的成员，在许多类型的癌症中都会增加。然而，尚不清楚survivin增加是否与口腔鳞状细胞癌（OSCC）相关，以及可能涉及哪些机制。在本研究中，我们通过免疫组织化学染色检查了OSCC与正常口腔组织中survivin表达的比较。结果表明，与正常口腔组织相比，OSCC中不仅总survivin增加，而且survivin的亚细胞位置也发生改变。在大多数正常口腔组织中，生存素染色要么呈阴性，要么呈细胞质阳性/细胞核阴性；而在大多数 OSCC 组织中，生存素染色呈核阳性。统计分析表明，核存活蛋白（而不是总存活蛋白或细胞质存活蛋白）与肿瘤 TNM 分期和分化等级相关。体外分析一致表明，生存素存在于正常人口腔激动细胞 (HOK) 细胞的细胞质中；而 OSCC HN6 细胞中它位于细胞核中。重要的是，用 HDAC 抑制剂曲古抑菌素 A (TSA) 处理 HOK 细胞会诱导生存素乙酰化并促进其核定位。此外，OSCC细胞中的核生存素在其C末端的K129处被乙酰化，这表明乙酰化对于生存素的核定位很重要。我们的研究表明，与 OSCC 的 TNM 分期和肿瘤分级相关的是核生存素，而不是总生存素或细胞质生存素。因此，我们建议将核生存素作为 OSCC 进展的预后标志物。
Defects in apoptotic pathway contribute to development and progression of oral cancer. Survivin, a member of the inhibitors of apoptosis protein (IAP) family, is increased in many types of cancers. However, it is unclear whether increased survivin is associated with oral squamous cell carcinomas (OSCC), and what mechanisms may involve in. In this study, we examined survivin expression in OSCC compared with normal oral tissues via immunohistochemical staining. The results showed that, not only total survivin is increased in OSCCs, but also the subcellular location of survivin is changed in OSCCs compared with normal oral tissues. In most of normal oral tissues, survivin staining was either negative, or cytoplasmic positive/nuclear negative; whereas in most of OSCC tissues, survivin staining was nuclear positive. Statistic analysis indicates that nuclear survivin, rather than total or cytoplasmic one, correlates with tumor TNM stage and differentiation grade. Consistently, in vitro analysis showed that survivin is in cytoplasm in normal human oral kinotinocyte (HOK) cells; whereas it is in nucleus in OSCC HN6 cells. Importantly, treatment of HOK cells with HDAC inhibitor Trichostatin A (TSA) induces survivin acetylation and promotes its nuclear localization. Moreover, nuclear survivin in OSCC cells was acetylated at K129 in its C-terminal, suggesting that the acetylation is important for nuclear location of survivin. Our study demonstrates that it is nuclear survivin, rather than total or cytoplasmic one, associates with TNM stage and tumor grade of OSCC. Thus, we propose nuclear survivin as a prognostic marker for the progression of OSCC.