Nuclear survivin promoted by acetylation is associated with the aggressive phenotype of oral squamous cell carcinoma.
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.
['Liu|Shuli|S|', 'Shi|Lei|L|', 'Yang|Xi|X|', 'Ye|Dongxia|D|', 'Wang|Tong|T|', 'Dong|Cunshan|C|', 'Guo|Wenzheng|W|', 'Liao|Yueling|Y|', 'Song|Hongyong|H|', 'Xu|Dongliang|D|', 'Hu|Jingzhou|J|', 'Zhang|Zhiyuan|Z|', 'Deng|Jiong|J|']
D000107:Acetylation D000328:Adult D000368:Aged D000369:Aged, 80 and over D002294:Carcinoma, Squamous Cell D002467:Cell Nucleus D005260:Female D015972:Gene Expression Regulation, Neoplastic D006801:Humans D051034:Inhibitor of Apoptosis Proteins D015603:Keratinocytes D008239:Lysine D008297:Male D008875:Middle Aged D009062:Mouth Neoplasms D010641:Phenotype D011379:Prognosis D021381:Protein Transport D012333:RNA, Messenger D013347:Subcellular Fractions D000077022:Survivin D015854:Up-Regulation
survivin acetylation apoptosis OSCC subcellular location tumor grade IHC