Exploring the mechanism of WWOX growth inhibitory effects on oral squamous cell carcinoma.

Exploring the mechanism of WWOX growth inhibitory effects on oral squamous cell carcinoma.
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探讨WWOX对口腔鳞状细胞癌生长抑制作用的机制。

DOI:
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发表时间:
2017
期刊:
影响因子:
2.9
通讯作者:
Liang Peng
Liang Peng
中科院分区:
医学4区
文献类型:
--
作者:
Wei Yang;Xiao;H. Yuan;Zhi;Shuang Gao;Liang Peng

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口腔鳞状细胞癌是世界上最常见的头颈部肿瘤之一。确诊为OSCC的患者预后较差。WW结构域氧化还原酶(WWOX)是一种候选肿瘤抑制基因,参与肿瘤的发生和发展。在OSCC和口腔白斑中发现了WWOX基因的缺失,但WWOX在OSCC中的功能和机制尚不清楚。因此,本研究探讨了WWOX在口腔鳞癌细胞中的作用。结果显示,WWOX表达的升高对三种口腔鳞癌细胞的生长均有抑制作用,其中以Tca8113细胞的抑制作用最为明显。此外,在Tca8113细胞中,WWOX过表达显著抑制集落形成,诱导细胞凋亡和细胞周期阻滞。微阵列分析、逆转录-定量聚合酶链反应和western blotting检测发现,WWOX过表达导致介导细胞外信号调节蛋白激酶/丝裂原活化蛋白激酶(ERK/MAPK)信号通路相关基因的差异表达。这些结果提示,WWOX基因的肿瘤抑制功能可能与ERK/MAPK信号通路的调控有关,从而为OSCC的治疗提供了新的靶点。
Oral squamous cell carcinoma (OSCC) is one of the most common types of head and neck neoplasms in the world. Patients diagnosed with OSCC exhibit a poor prognosis. WW domain-containing oxidoreductase (WWOX), as a candidate tumor-suppressor gene, is involved in the genesis and progression of tumors. The deletion of the WWOX gene has been identified in OSCC and oral leukoplakia, but the function and mechanism of WWOX in OSCC remain unknown. Therefore, the present study investigated the role of WWOX in oral squamous carcinoma cells. The results revealed that an elevation of WWOX expression had an inhibitory effect on the growth of three types of oral squamous carcinoma cells, with the most evident effect occurring in Tca8113 cells. Also, in the Tca8113 cells, WWOX overexpression significantly inhibited colony formation, and induced apoptosis and cell cycle arrest. Microarray analysis, reverse transcription-quantitative polymerase chain reaction and western blotting methods detected that WWOX overexpression contributed to the differential expression of the genes involved in mediating the extracellular-signal regulated protein kinase/mitogen-activated protein kinase (ERK/MAPK) signaling pathway. These results suggest that the tumor-suppressor function of the WWOX gene may be associated with the modulation of the ERK/MAPK signaling pathway, thus providing a novel target for OSCC therapy.
DOI: --
发表时间: 2010-08
期刊: Molecular Vision
影响因子: 2.2
作者:
Z. Wang;P. Reinach;Fan Zhang;Kati-Sisko Vellonen;A. Urtti;H. Turner;J. Wolosin
通讯作者: Z. Wang;P. Reinach;Fan Zhang;Kati-Sisko Vellonen;A. Urtti;H. Turner;J. Wolosin