Urokinase-type plasminogen activator receptor signaling is critical in nasopharyngeal carcinoma cell growth and metastasis
Urokinase-type plasminogen activator receptor signaling is critical in nasopharyngeal carcinoma cell growth and metastasis
复制标题
尿激酶型纤溶酶原激活剂受体信号传导在鼻咽癌细胞生长和转移中至关重要
DOI：
10.4161/cc.28921
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发表时间：
2014-06-15
期刊：
影响因子：
4.3
通讯作者：
Qian, Chao-Nan
中科院分区：
文献类型：
--
作者：
Bao, Ying-Na;Cao, Xue;Qian, Chao-Nan
鼻咽癌（NPC）是中国南方和东南亚地区最常见的恶性肿瘤之一，也是头颈部癌症中转移率最高的。NPC进展的潜在机制仍然知之甚少。对18例NPC和18例非癌鼻咽组织的全基因组表达谱分析以及NPC细胞和组织中的GeneGo通路分析和表达验证揭示了尿激酶型纤溶酶原激活物受体（uPAR）在NPC进展中的潜在作用，这在NPC中尚未研究。我们观察到uPAR在低分化、高转移的NPC细胞中的表达比低转移或分化的NPC细胞中的表达增加。体外研究表明，uPAR调节NPC细胞的生长、集落形成、迁移和侵袭，并促进上皮-间质转化（EMT）。其他肿瘤异种移植和自发转移实验表明，uPAR促进体内NPC细胞生长和转移。JAK-STAT通路参与NPC细胞中uPAR调节的信号传导，如通过免疫印迹所确定的。此外，在用Jak 1/Jak 2抑制剂INCB 018424处理后，uPAR介导的生长和运动被部分消除。我们在uPAR过表达的NPC细胞中抑制uPA表达，发现uPAR介导的细胞生长和运动并不完全依赖于uPA。总之，uPAR是NPC进展的重要调节剂，可以作为有前途的治疗靶点。
Nasopharyngeal carcinoma (NPC) is one of the most common malignancies in southern China and Southeast Asia, with the highest metastasis rate among head and neck cancers. The mechanisms underlying NPC progression remain poorly understood. Genome-wide expression profiling on 18 NPC vs. 18 noncancerous nasopharyngeal tissues together with GeneGo pathway analysis and expression verification in NPC cells and tissues revealed a potential role of urokinase-type plasminogen activator receptor (uPAR) in NPC progression, which has not been investigated in NPC. We then observed that uPAR expression is increased in poorly differentiated, highly metastatic NPC cells compared with lowly metastatic cells or differentiated NPC cells. In vitro studies demonstrated that uPAR regulates NPC cell growth, colony formation, migration, and invasion and promotes the epithelial–mesenchymal transition (EMT). Additional tumor xenograft and spontaneous metastasis experiments revealed that uPAR promotes NPC cell growth and metastasis in vivo. The JAK–STAT pathway is involved in uPAR-regulated signaling in NPC cells as determined by immunoblotting. Moreover, uPAR-mediated growth and motility is partially abolished upon treatment with the Jak1/Jak2 inhibitor INCB018424. We suppressed uPA expression in uPAR-overexpressing NPC cells and found that uPAR-mediated cellular growth and motility is not exclusively dependent on uPA. In summary, uPAR is a significant regulator of NPC progression and could serve as a promising therapeutic target.