JAG1 Is Associated with Poor Survival through Inducing Metastasis in Lung Cancer.
JAG1 Is Associated with Poor Survival through Inducing Metastasis in Lung Cancer.
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DOI：
10.1371/journal.pone.0150355
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Yu SL
中科院分区：
文献类型：
--
作者：
Chang WH;Ho BC;Hsiao YJ;Chen JS;Yeh CH;Chen HY;Chang GC;Su KY;Yu SL
JAG1 是一种 Notch 配体，在多种信号通路中发挥着关键作用。然而，JAG1 在非小细胞肺癌 (NSCLC) 中的功能尚未得到彻底研究。通过比较具有不同侵袭能力的细胞系对中基因转录的RNA谱，我们确定JAG1是肺癌中潜在的转移增强子。 JAG1在肺癌细胞上的异位表达增强了细胞的迁移和侵袭以及体外和体内的转移。相反，在高侵袭性癌细胞中用 siRNA 敲低 JAG1 会导致迁移和侵袭减少。在临床分析中，20 名鳞状细胞癌 (SCC) 患者中，有 14 名患者的肿瘤中 JAG1 mRNA 表达高于邻近正常组织。 JAG1 转录较高的鳞状细胞癌患者的总生存率低于 JAG1 转录低的患者。微阵列分析表明，JAG1 转录的强制执行与 HSPA2 RNA 转录的升高相关，这在促进癌细胞迁移和侵袭中发挥了作用。总之，这是第一项证明 JAG1 可能作为潜在预后标志物并且 JAG1/HSPA2 轴至少部分介导肺癌恶性肿瘤的研究。
JAG1 is a Notch ligand that plays a critical role in multiple signaling pathways. However, the functionality of JAG1 in non-small cell lung cancer (NSCLC) has not been investigated thoroughly. By comparison of gene transcripted RNA profiles in the cell line pair with differential invasion ability, we identified JAG1 as a potential metastasis enhancer in lung cancer. Ectopic expression of JAG1 on lung cancer cells enhanced cell migration and invasion as well as metastasis in vitro and in vivo. Conversely, knockdown of JAG1 with siRNA in highly invasive cancer cells led to the reduction of migration and invasion. In clinical analysis, JAG1 mRNA expression was higher in tumors than in adjacent normal tissues in 14 of 20 patients with squamous cell carcinoma (SCC). SCC patients with higher JAG1 transcription had poor overall survival than those with low-transcripted JAG1. Microarray analysis indicated that the enforced JAG1 transcription was associated with an elevated HSPA2 RNA transcription, which played a role in promoting cancer cell migration and invasion. In conclusion, this is the first study that demonstrated that JAG1 might act as a potential prognostic marker and JAG1/HSPA2 axis mediates lung cancer malignancy at least partly.