ELTD1 facilitates glioma proliferation, migration and invasion by activating JAK/STAT3/HIF-1α signaling axis
ELTD1 facilitates glioma proliferation, migration and invasion by activating JAK/STAT3/HIF-1α signaling axis
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ELTD1通过激活JAK/STAT3/HIF-1α信号轴促进胶质瘤增殖、迁移和侵袭
DOI：
10.1038/s41598-019-50375-x
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发表时间：
2019-09-25
影响因子：
4.6
通讯作者：
Xiong, Nanxiang
中科院分区：
文献类型：
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作者：
Li, Junjun;Shen, Jianying;Xiong, Nanxiang
在几种类型的癌症中已经报道了肿瘤细胞中ELTD 1（[1号染色体上的表皮生长因子（EGF）、latrophilin和7个跨膜结构域1]）的上调，并且与癌症预后不良相关。然而，ELTD 1在胶质瘤进展中的作用仍然未知。在这项研究中，我们研究了ELTD 1在人脑胶质瘤细胞系和16个不同级别的人脑胶质瘤中的表达水平。使用定量聚合酶链反应（qRT-PCR）、蛋白质印迹、细胞增殖测定、基质胶迁移和侵袭测定以及脑原位异种移植物测量ELTD 1在胶质瘤细胞中的分子效应。我们发现ELTD 1的高表达水平与人脑胶质瘤的进展和不良预后呈正相关。从机制上讲，ELTD 1激活JAK/STAT 3/HIF-1 α信号轴，p-STAT 3与HIF-1 α结合。总之，我们的数据提供了一个合理的机制ELTD 1调节胶质瘤的进展，并建议ELTD 1可能代表一个潜在的治疗目标，在预防和治疗胶质瘤。
The upregulation of ELTD1 ([epidermal growth factor (EGF), latrophilin and seven transmembrane domain-containing 1] on chromosome 1) in tumor cells has been reported in several types of cancer and correlates with poor cancer prognosis. However, the role of ELTD1 in glioma progression remains unknown. In this study, we examined ELTD1 expression levels in human glioma cell lines and in sixteen human gliomas of different grades. The molecular effects of ELTD1 in glioma cells were measured using quantitative polymerase chain reaction (qRT-PCR), Western blotting, Cell proliferation assays, Matrigel migration and invasion assays and brain orthotopic xenografts. We found that high expression levels of ELTD1 were positively associated with cancer progression and poor prognosis in human glioma. Mechanistically, ELTD1 activated the JAK/STAT3/HIF-1 alpha signaling axis and p-STAT3 bound with HIF-1 alpha. Taken together, our data provide a plausible mechanism for ELTD1-modulated glioma progression and suggest that ELTD1 may represent a potential therapeutic target in the prevention and therapy of glioma.