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果糖-1,6-二磷酸醛缩酶C表达的抑制作为晚期口腔鳞状细胞癌的预测指标

Suppression of fructose-bisphosphate aldolase C expression as a predictor of advanced oral squamous cell carcinoma.

作者信息

Li Yue-Ju, Huang Tse-Hung, Hsiao Michael, Lin Been-Ren, Cheng Shih-Jung, Yang Cheng-Ning, Lai Wei-Ting, Wu Tai-Sheng, Fan Jia-Ruei, Kuo Mark Yen-Ping, Chang Cheng-Chi

机构信息

Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan.

Angiogenesis Research Center, National Taiwan University, Taipei, Taiwan.

出版信息

Head Neck. 2016 Apr;38 Suppl 1:E1075-85. doi: 10.1002/hed.24161. Epub 2015 Nov 13.

Abstract

BACKGROUND

Glycolysis machinery regulates cancer cell behavior. However, the roles of these glycolysis enzymes in oral squamous cell carcinoma (OSCC) progression remain unknown.

METHODS

Fructose-bisphosphate aldolase C (ALDOC) expression in OSCC patients and cell lines was detected using quantitative real-time polymerase chain reaction (PCR). The functions of ALDOC in migration and invasion were determined using gain and loss of function approaches. An orthotopic OSCC animal model was performed to investigate the effects of ALDOC on metastasis and tumorigenesis in vivo.

RESULTS

ALDOC expression is negatively significantly correlated with clinical outcome and cell migration in vitro and in vivo. ALDOC blocks adenosine triphosphate generation and lactate production, and mutation constructs of Arg42 and Lys146 functionally restore ALDOC-inhibited cell migration and invasion.

CONCLUSION

ALDOC functions as an OSCC prognosis marker clinically, and suppresses migration and invasion by its catalytic domain of Arg42 and Lys146. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1075-E1085, 2016.

摘要

背景

糖酵解机制调控癌细胞行为。然而,这些糖酵解酶在口腔鳞状细胞癌(OSCC)进展中的作用仍不清楚。

方法

采用定量实时聚合酶链反应(PCR)检测OSCC患者及细胞系中果糖二磷酸醛缩酶C(ALDOC)的表达。采用功能获得和功能缺失方法确定ALDOC在迁移和侵袭中的作用。建立原位OSCC动物模型以研究ALDOC在体内对转移和肿瘤发生的影响。

结果

ALDOC表达与临床结局以及体内外细胞迁移呈显著负相关。ALDOC阻断三磷酸腺苷生成和乳酸产生,并且Arg42和Lys146的突变构建体在功能上恢复了ALDOC抑制的细胞迁移和侵袭。

结论

ALDOC在临床上作为OSCC预后标志物发挥作用,并通过其Arg42和Lys146催化结构域抑制迁移和侵袭。©2015威利期刊公司。头颈外科38: E1075 - E1085, 2016。

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