EFEMP1 promotes the migration and invasion of osteosarcoma via MMP-2 with induction by AEG-1 via NF-κB signaling pathway.
EFEMP1 promotes the migration and invasion of osteosarcoma via MMP-2 with induction by AEG-1 via NF-κB signaling pathway.
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DOI：
10.18632/oncotarget.3691
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发表时间：
2015-06-10
期刊：
影响因子：
--
通讯作者：
Wang LT
中科院分区：
文献类型：
--
作者：
Wang Z;Cao CJ;Huang LL;Ke ZF;Luo CJ;Lin ZW;Wang F;Zhang YQ;Wang LT
含表皮生长因子的纤维蛋白样细胞外基质蛋白1（EFEMP 1）在骨肉瘤中的作用仍不清楚。然后应用EFEMP 1 siRNA、质粒转染和加入纯化的EFEMP 1蛋白的方法对人骨肉瘤细胞株进行转染，并对113例骨肉瘤组织进行免疫组化检测，结果表明EFEMP 1是骨肉瘤预后不良的指标; EFEMP 1在骨肉瘤中特异性上调，并与骨肉瘤的侵袭和转移相关。同时，我们发现EFEMP 1对MMP-2有直接的调节作用。此外，我们还首次发现致癌AEG-1对EFEMP 1有明显的诱导作用。选择性NF-κB抑制剂（PDTC）可抑制骨肉瘤细胞EFEMP 1的表达。NF-κB通路可能是AEG-1诱导EFEMP 1表达的有效途径之一。因此，我们认为EFEMP 1在AEG-1和MMP-2之间起着介导作用。NF-κB信号通路在此过程中起重要作用。综上所述，EFEMP 1与骨肉瘤患者的侵袭、转移和不良预后有关。EFEMP 1可能间接促进MMP-2的表达，为AEG-1在肿瘤转移中的作用提供了可能的解释。NF-κB通路可能是AEG-1诱导EFEMP 1表达的有效途径之一。
The role of epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) in osteosarcoma remains unknown. Then applying EFEMP1 siRNA, plasmids transfection and adding purified EFEMP1 protein in human osteosarcoma cell lines, and using immunohistochemistry on 113 osteosarcoma tissues, demonstrated that EFEMP1 was a poor prognostic indicator of osteosarcoma; EFEMP1 was specifically upregulated in osteosarcoma and associated with invasion and metastasis in vitro and in vivo. At the same time, we found a direct regulatory effect of EFEMP1 on MMP-2. Moreover, we firstly found the marked induction of EFEMP1 by oncogenic AEG-1. And EFEMP1 expression was inhibited by the selective inhibitor of NF-κB (PDTC) in osteosarcoma cells. Then we thought that NF-κB pathways might be one of the effective ways which EFEMP1 was induced by AEG-1. Thus, we suggested that EFEMP1 played a part as the mediator between AEG-1 and MMP-2. And NF-κB signaling pathway played an important role in this process. In summary, EFEMP1 was associated with invasion, metastasis and poor prognosis of osteosarcoma patients. EFEMP1 might indirectly enhance the expression of MMP-2, providing a potential explanation for the role of AEG-1 in metastasis. NF-κB pathways might be one of the effective ways which EFEMP1 was induced by AEG-1.