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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Zhuo Wang1,*, Chuang-Jie Cao1,*, Lei-Lei Huang1,*, Zun-Fu Ke1, Can-Jiao Luo1, Zhong-Wei Lin2, Fen Wang1, Yuan-Qi Zhang3 and Lian-Tang Wang1
1 Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
2 Department of Cardiology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China
3 Department of Vascular Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang, China
* These authors have contributed equally to this work
Lian-Tang Wang, email:
Keywords: osteosarcoma, AEG-1, EFEMP1, MMP-2, NF-κB
Received: January 04, 2015 Accepted: March 03, 2014 Published: March 29, 2015
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.
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