Reduced CTGF expression promotes cell growth, migration, and invasion in nasopharyngeal carcinoma.

Reduced CTGF expression promotes cell growth, migration, and invasion in nasopharyngeal carcinoma.
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CTGF 表达减少可促进鼻咽癌细胞生长、迁移和侵袭。

DOI:
10.1371/journal.pone.0064976
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Fang W
Fang W
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Zhen Y;Ye Y;Yu X;Mai C;Zhou Y;Chen Y;Yang H;Lyu X;Song Y;Wu Q;Fu Q;Zhao M;Hua S;Wang H;Liu Z;Zhang Y;Fang W

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CTGF在不同类型的癌症中的作用不同。本研究旨在探讨CTGF在鼻咽癌(NPC)中的表达及其与肿瘤进展和预后的关系。在NPC组织和细胞、鼻咽(NP)组织和NP 69细胞中检测CTGF表达水平。探讨CTGF表达对细胞增殖、迁移、侵袭和细胞周期的影响及其分子机制。与永生化人鼻咽上皮细胞系NP 69相比,NPC细胞表现出CTGF mRNA表达降低。同样,CTGF在mRNA和蛋白水平上在NPC中与正常组织相比被观察到下调。此外,CTGF降低与NPC的进展呈负相关。敲低CTGF表达可促进殖民地形成、细胞迁移、侵袭和G1/S期细胞转换。机制分析显示,CTGF抑制激活FAK/PI 3 K/AKT及其下游信号调节细胞周期、上皮-间质转化(EMT)和MMPs。最后,DNA甲基化微阵列显示CTGF启动子缺乏高甲基化,提示其他机制与NPC中CTGF的抑制有关。我们的研究表明,CTGF的表达减少,促进细胞增殖,迁移,侵袭和细胞周期的进展,通过FAK/PI 3 K/AKT,EMT和MMP途径在NPC。
The role of CTGF varies in different types of cancer. The purpose of this study is to investigate the involvement of CTGF in tumor progression and prognosis of human nasopharyngeal carcinoma (NPC). CTGF expression levels were examined in NPC tissues and cells, nasopharynx (NP) tissues, and NP69 cells. The effects and molecular mechanisms of CTGF expression on cell proliferation, migration, invasion, and cell cycle were also explored. NPC cells exhibited decreased mRNA expression of CTGF compared to immortalized human nasopharyngeal epithelial cell line NP69. Similarly, CTGF was observed to be downregulated in NPC compared to normal tissues at mRNA and protein levels. Furthermore, reduced CTGF was negatively associated with the progression of NPC. Knocking down CTGF expression enhanced the colony formation, cell migration, invasion, and G1/S cell cycle transition. Mechanistic analysis revealed that CTGF suppression activated FAK/PI3K/AKT and its downstream signals regulating the cell cycle, epithelial-mesenchymal transition (EMT) and MMPs. Finally, DNA methylation microarray revealed a lack of hypermethylation at the CTGF promoter, suggesting other mechanisms are associated with suppression of CTGF in NPC. Our study demonstrates that reduced expression of CTGF promoted cell proliferation, migration, invasion and cell cycle progression through FAK/PI3K/AKT, EMT and MMP pathways in NPC.
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