Numb inhibits epithelial-mesenchymal transition via RBP-Jk-dependent Notch1/PTEN/FAK signaling pathway in tongue cancer
Numb inhibits epithelial-mesenchymal transition via RBP-Jk-dependent Notch1/PTEN/FAK signaling pathway in tongue cancer
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DOI：
10.1186/s12885-019-5605-5
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发表时间：
2019-04-25
期刊：
影响因子：
3.8
通讯作者：
Li, Zan
中科院分区：
文献类型：
--
作者：
Li, Jin-Yun;Huang, Wen-Xiao;Li, Zan
口腔癌是世界上第六大常见的实体癌，其中舌鳞状细胞癌（tongue squamous cell carcinoma，TSCC）是最常见的口腔癌。方法采用RT-qPCR方法检测TSCC中Numb、PTEN和Notch 1基因以及EMT相关基因的mRNA水平。Western blot法检测这些基因的蛋白水平。此外，我们还通过MTT法检测细胞增殖，并通过transwell侵袭实验和伤口愈合实验分别检测细胞的侵袭和迁移能力。为了探讨PTEN的作用，其抑制剂VO-Ohpic三水合物被用来处理SCC-4和CAL-27 cells.ResultsWe发现，Numb表达下调SCC-9和CAL-27细胞相比，NHOK细胞。相反，SCC-9和CAL-27细胞中Notch 1的水平高于NHOK细胞。Numb过表达可通过调控Notch 1信号通路和EMT相关基因的表达，抑制SCC-9和CAL-27细胞的增殖、迁移和侵袭。相反，我们观察到RBP-J敲低对SCC-9和CAL-27细胞的增殖、迁移和侵袭具有抑制作用。在Numb过表达或RBP-J敲低的细胞中，p-FAK和EMT相关基因受到显著调节。结论我们的研究结果为了解TSCC的转移提供了新的机制，并有助于制定治疗舌癌的治疗策略。
BackgroundOral cancer has been estimated as the sixth most frequent solid cancer all over the world, in which tongue squamous cell carcinoma (TSCC) is the most common type of oral cancers. However, the mechanism of TSCC metastasizing to lymph node and distant sites has not been completely understood.MethodsIn this study, RT-qPCR method was used to detect the mRNA level of Numb, PTEN and Notch1 genes, as well as EMT-associated genes. Western blot assay was utilized to detect protein level of these genes. In addition, we determined cell proliferation by MTT assay and employed transwell invasion assay and wound healing assay to probe the abilities of invasion and migration, respectively. To investigate the role of PTEN, its inhibitor VO-Ohpic trihydrate was used to treat SCC-4 and CAL27 cells.ResultsWe found that Numb expression was downregulated in SCC-9 and CAL-27 cells compared to NHOK cells. Instead, Notch1 level in SCC-9 and CAL-27 cells were higher than that in NHOK cells. Furthermore, the results showed that Numb overexpression significantly suppressed proliferation, migration and invasion of SCC-9 and CAL-27 cells via regulating Notch1 signaling and EMT-related genes expression. By contrast, we observed that RBP-J knockdown had an inhibitory role in proliferation, migration and invasion of SCC-9 and CAL-27 cells. In cells with Numb overexpression or RBP-J knockdown, p-FAK and EMT-related genes were remarkably regulated.ConclusionsOur findings provide new mechanism of understanding the metastasis of TSCC and help develop therapeutic strategies for treating tongue cancer.