BMP2 promotes proliferation and invasion of nasopharyngeal carcinoma cells via mTORC1 pathway.
BMP2 promotes proliferation and invasion of nasopharyngeal carcinoma cells via mTORC1 pathway.
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BMP2通过mTORC1通路促进鼻咽癌细胞增殖和侵袭
DOI：
10.18632/aging.101230
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发表时间：
2017-04
期刊：
影响因子：
--
通讯作者：
Mai SJ
中科院分区：
文献类型：
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作者：
Wang MH;Zhou XM;Zhang MY;Shi L;Xiao RW;Zeng LS;Yang XZ;Zheng XFS;Wang HY;Mai SJ
骨形态发生蛋白 -2（BMP2）是一种分泌性蛋白，在多种癌症中高表达，并促进细胞增殖、迁移、侵袭性、移动性、转移以及上皮 - 间质转化（EMT）。然而，其在鼻咽癌（NPC）中的临床意义和生物学功能至今仍不清楚。在我们先前的一项全基因组转录组分析中，首次在鼻咽癌（NPC）细胞系中观察到BMP2的上调。在本研究中，通过实时定量聚合酶链反应（qRT - PCR）检测BMP2 mRNA，数据显示与非癌性鼻咽样本相比，它在鼻咽癌（NPC）中表达上调。对鼻咽癌（NPC）标本进行的免疫组织化学（IHC）分析表明，BMP2高表达与鼻咽癌（NPC）患者的临床分期、远处转移以及较短的生存期显著相关。此外，BMP2在鼻咽癌（NPC）细胞中的过表达促进了细胞增殖、迁移、侵袭以及上皮 - 间质转化（EMT）。从机制上讲，BMP2过表达提高了哺乳动物雷帕霉素靶蛋白（mTOR）、核糖体蛋白S6激酶（S6K）和真核起始因子4E结合蛋白1（4EBP1）的磷酸化蛋白水平。相应地，mTORC1抑制剂雷帕霉素阻断了BMP2对鼻咽癌（NPC）细胞增殖和侵袭的作用。总之，我们的研究结果表明，鼻咽癌（NPC）中BMP2的过表达通过mTORC1信号通路增强了肿瘤细胞的增殖、侵袭和上皮 - 间质转化（EMT）。
Bone morphogenetic protein-2 (BMP2) is a secreted protein that highly expressed in a variety of cancers and contributes to cell proliferation, migration, invasiveness, mobility, metastasis and EMT. However, its clinical significance and biological function in nasopharyngeal carcinoma (NPC) remain unknown up to now. Up-regulation of BMP2 was first observed in NPC cell lines by a genome-wide transcriptome analysis in our previous study. In this study, BMP2 mRNA was detected by qRT-PCR and data showed that it was upregulated in NPC compared with non-cancerous nasopharynx samples. Immunohistochemistry (IHC) analysis in NPC specimens revealed that high BMP2 expression was significantly associated with clinical stage, distant metastasis and shorter survival of NPC patients. Moreover, overexpression of BMP2 in NPC cells promoted cell proliferation, migration, invasiveness and epithelial-mesenchymal transition (EMT). Mechanistically, BMP2 overexpression increase phosphorylated protein level of mTOR, S6K and 4EBP1. Correspondingly, mTORC1 inhibitor rapamycin blocked the effect of BMP2 on NPC cell proliferation and invasion. In conclusion, our results suggest that BMP2 overexpression in NPC enhances proliferation, invasion and EMT of tumor cells through the mTORC1 signaling pathway.