title: EFEMP1 promotes the migration and invasion of osteosarcoma via MMP-2 with induction by AEG-1 via NF-κB signaling pathway.
abstract: 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.
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Chuang-Jie
authors.initials: CJ
authors.lastname: Cao
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Lei-Lei
authors.initials: LL
authors.lastname: Huang
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Zun-Fu
authors.initials: ZF
authors.lastname: Ke
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Can-Jiao
authors.initials: CJ
authors.lastname: Luo
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China.
authors.forename: Zhong-Wei
authors.initials: ZW
authors.lastname: Lin
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Vascular Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang, China.
authors.forename: Yuan-Qi
authors.initials: YQ
authors.lastname: Zhang
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Lian-Tang
authors.initials: LT
authors.lastname: Wang
mesh_terms: D000328:Adult; D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism*; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D016601:RNA-Binding Proteins; D015398:Signal Transduction; D014162:Transfection; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D015815:Cell Adhesion Molecules; C119630:EFEMP1 protein, human; D016326:Extracellular Matrix Proteins; C483039:MTDH protein, human; D008565:Membrane Proteins; D016328:NF-kappa B; D016601:RNA-Binding Proteins; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
keywords: AEG-1; EFEMP1; MMP-2; NF-κB; osteosarcoma