title: Nuclear survivin promoted by acetylation is associated with the aggressive phenotype of oral squamous cell carcinoma.
abstract: 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.
authors.affiliation: a Department of Oral and Maxillofacial-Head and Neck Oncology , Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai , China.|b Shanghai Key Laboratory of Stomatology , Shanghai , China.
authors.forename: Shuli
authors.initials: S
authors.lastname: Liu
authors.affiliation: c Department of Oral and Maxillofacial Surgery , Gansu Provincial Hospital , Gansu , China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.affiliation: a Department of Oral and Maxillofacial-Head and Neck Oncology , Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai , China.|b Shanghai Key Laboratory of Stomatology , Shanghai , China.
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
authors.affiliation: a Department of Oral and Maxillofacial-Head and Neck Oncology , Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai , China.|b Shanghai Key Laboratory of Stomatology , Shanghai , China.
authors.forename: Dongxia
authors.initials: D
authors.lastname: Ye
authors.affiliation: d Key Laboratory of Cell Differentiation and Apoptosis of Chinese Minister of Education , Shanghai Jiao Tong University School of Medicine , Shanghai , China.
authors.forename: Tong
authors.initials: T
authors.lastname: Wang
authors.affiliation: e Department of Oral and Maxillofacial Surgery , Double Mineral Hospital , Shuangyashan , Heilongjiang , China.
authors.forename: Cunshan
authors.initials: C
authors.lastname: Dong
authors.affiliation: d Key Laboratory of Cell Differentiation and Apoptosis of Chinese Minister of Education , Shanghai Jiao Tong University School of Medicine , Shanghai , China.
authors.forename: Wenzheng
authors.initials: W
authors.lastname: Guo
authors.affiliation: d Key Laboratory of Cell Differentiation and Apoptosis of Chinese Minister of Education , Shanghai Jiao Tong University School of Medicine , Shanghai , China.
authors.forename: Yueling
authors.initials: Y
authors.lastname: Liao
authors.affiliation: d Key Laboratory of Cell Differentiation and Apoptosis of Chinese Minister of Education , Shanghai Jiao Tong University School of Medicine , Shanghai , China.
authors.forename: Hongyong
authors.initials: H
authors.lastname: Song
authors.affiliation: d Key Laboratory of Cell Differentiation and Apoptosis of Chinese Minister of Education , Shanghai Jiao Tong University School of Medicine , Shanghai , China.
authors.forename: Dongliang
authors.initials: D
authors.lastname: Xu
authors.affiliation: a Department of Oral and Maxillofacial-Head and Neck Oncology , Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai , China.|b Shanghai Key Laboratory of Stomatology , Shanghai , China.
authors.forename: Jingzhou
authors.initials: J
authors.lastname: Hu
authors.affiliation: a Department of Oral and Maxillofacial-Head and Neck Oncology , Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai , China.|b Shanghai Key Laboratory of Stomatology , Shanghai , China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: d Key Laboratory of Cell Differentiation and Apoptosis of Chinese Minister of Education , Shanghai Jiao Tong University School of Medicine , Shanghai , China.|f Shanghai Key Laboratory for Tumor Microenvironment and Inflammation , Shanghai Jiao Tong University School of Medicine , Shanghai , China.|g Translation Medicine Center, Shanghai Chest Hospital , Shanghai Jiao Tong University , Shanghai , China.
authors.forename: Jiong
authors.initials: J
authors.lastname: Deng
mesh_terms: D000107:Acetylation; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002467:Cell Nucleus / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D008239:Lysine / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D010641:Phenotype; D011379:Prognosis; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D000077022:Survivin; D015854:Up-Regulation / Q000235:genetics
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D012333:RNA, Messenger; D000077022:Survivin; D008239:Lysine
keywords: IHC; OSCC; acetylation; apoptosis; subcellular location; survivin; tumor grade