EFEMP1 promotes the migration and invasion of osteosarcoma via MMP-2 with induction by AEG-1 via NF-κB signaling pathway

Wang, Zhuo; Cao, Chuang-Jie; Huang, Leilei; Ke, Zunfu; Chen, Luo; Lin, Zhongwei; Wang, Fen; Zhang, Yuanqi; Wang, Liantang

doi:10.18632/oncotarget.3691

Cited by 54 publications

(49 citation statements)

References 41 publications

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“…Through previous studies, we found that EFEMP1 was involved in the regulation of many biological processes in carcinoma, suggesting that EFEMP1 may play an important role in the development of HCC. When the transcription of EFEMP1 was inhibited, how did it cause phenotypic changes in HCC cells, and by what kind of signaling pathway to affect HCC?…”

Section: Resultsmentioning

confidence: 96%

Epidermal growth factor‐containing fibulin‐like extracellular matrix protein 1 (EFEMP1) suppressed the growth of hepatocellular carcinoma cells by promoting Semaphorin 3B(SEMA3B)

Duan

Jiang

et al. 2019

Cancer Medicine

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Aim Epidermal growth factor‐containing fibulin‐like extracellular matrix protein 1(EFEMP1) has been found to be involved in the occurrence and development of many cancers. The relationship between EFEMP1 and the development of hepatocellular carcinoma (HCC) and the molecular mechanism are not fully understood. Methods Real‐time polymerase chain reaction (PCR) and tissue microarray were used to detect the expression of EFEMP1 in HCC cell lines and tissue. Methylation‐specific PCR assay was used to measure the methylation level of EFEMP1 in HCC cell lines and tissue. To study the function of EFEMP1 on cell function, Huh7 and HepG2 were infected with lentiviral particles expressing EFEMP1. MTT assay and colony formation assay were used to examine the effect of EFEMP1 on cell proliferation. Annexin‐VAPC/7‐AAD double were used to detect the effect of EFEMP1 on cell apoptosis. To further detect the effect of EFEMP1 on the development of HCC in vivo, we performed the tumor formation experiment in nude mice. Gene chip was used to detect the expression profile of Huh7 and HepG2 overexpressing EFEMP1. To further screen out the differences, GO analysis and pathway analysis were performed. To study the effects of SEMA3B, specific siRNA was used to inhibit the expression of SEMA3B. Chi‐squared test and rank sum test were used to analyze the relationship between EFEMP1 expression and HCC clinical characteristic. Results The study found that the expression of EFEMP1 was significantly decreased in HCC cell lines and HCC tissues. The expression level of EFEMP1 was related to the TNM (the extent of the tumor, the extent of spread to the lymph nodes, the presence of metastasis) stage and the prognosis of patients with HCC. The decrease of protein expression suggested that the patient prognosis was worse, and the protein level of EFEMP1 may be an independent factor in the prognosis of HCC patients. Promoter methylation may be one of the reasons for EFEMP1 inhibition. EFEMP1 could inhibit the proliferation of HCC cells and promoted the apoptosis of HCC cells to regulate the development of HCC. And EFEMP1 promoted the apoptosis of HCC cells mainly through the mitochondrial apoptosis pathway. EFEMP1 may inhibit the proliferation of HCC cells through the SEMA3B gene in the Axon guidance pathway. Conclusion In summary, our research revealed the regulation of EFEMP1 on cell proliferation and apoptosis in HCC. EFEMP1 may suppress the growth of HCC cells by promoting SEMA3B.

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Section: Resultsmentioning

confidence: 96%

Epidermal growth factor‐containing fibulin‐like extracellular matrix protein 1 (EFEMP1) suppressed the growth of hepatocellular carcinoma cells by promoting Semaphorin 3B(SEMA3B)

Duan

Jiang

et al. 2019

Cancer Medicine

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“…As a downstream target gene of Ha-ras and c-myc, AEG-1 mediats its tumor promoting effects [25]. Recent reports has shown that AEG-1 plays as a key converging point in oncogenic signaling pathways including the NF-kB pathway, the PI3K/AKT pathway, the Wnt pathway [9,26,27]. Through activating the nuclear factor kappaB (NF-kB) signaling pathway, AEG-1 induces increased anchorage-independent growth and invasiveness of tumor cells [28].…”

Section: Discussionmentioning

confidence: 99%

Interaction with AEG-1 and MDM2 is associated with glioma development and progression and correlates with poor prognosis

Ding

Zhang

et al. 2019

Cell Cycle

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Glioma is the most common central nervous system tumor with poor prognosis. The AEG-1 (Astrocyte Elevated Gene 1) gene displays oncogenic characteristics, including proliferation, metastasis, chemoresistance, invasion, and evasion of apoptosis, and is strongly linked to the occurrence of glioma. Here, we elucidated the potential contribution of AEG-1 in human glioma pathogenesis. In glioma cells, AEG-1 could directly interact with Murine Double Minute-2 (MDM2) protein resulting in MDM2-p53-mediated cell proliferation and apoptosis. MDM2 is being revealed as an oncoprotein, which is involved in many human cancers progression. By immunohistochemical and a multivariate analysis, expressions of AEG-1 and MDM2 were elevated in glioma and high AEG-1 and MDM2 expressions were showed to be correlated with poor prognosis. AEG-1-MDM2 interaction prolonged stabilization of MDM2 where AEG-1 inhibited ubiquitination and subsequent proteasome-mediated degradation of MDM2 protein. Moreover, slicing AEG-1 blocked MDM2 expression and then impacted MDM2-p53 pathway that influenced cell proliferation and apoptosis. These findings uncover a novel AEG-1-MDM2 interplay by which AEG-1 augments glioma progression and reveal a viable potential therapy for the treatment of glioma patients. ARTICLE HISTORY

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“…Epidermal growth factor‐containing fibulin‐like ECM protein 1 (EFEMP1, also called fibulin‐3) is reported to be upregulated in OS. The overexpression of EFEMP1 upregulates the expression of MMP‐2 and contributes to the migratory and invasive capability of OS cells by binding the EGF receptor and activating the MAPK and Akt pathways . Wang et al.…”

Section: Mmps Promote Osteosarcoma Progressionmentioning

confidence: 99%

“…also speculated that EFEMP1 is a downstream target molecule of astrocyte elevated gene‐1 (AEG‐1, also known as metadherin or lyric) that is highly expressed in OS. They considered that AEG‐1 mediates OS progression and metastasis through upregulating MMP‐2 expression via activation of EFEMP1 by NF‐κB signaling pathway . B7‐H3 is a member of the B7‐family of costimulatory molecules, which has been shown to promote OS cell invasion, at least in part by upregulating MMP‐2 .…”

Section: Mmps Promote Osteosarcoma Progressionmentioning

confidence: 99%

Pathological and therapeutic aspects of matrix metalloproteinases: Implications in osteosarcoma

Tang¹,

Tang²,

Jiang³

et al. 2019

Asia-Pac J Clncl Oncology

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Osteosarcoma (OS) is one of the most common malignant bone tumors in children and adolescents, and the eighth leading form of childhood cancer. Matrix metalloproteinases (MMPs) are proteolytic enzymes implicated in certain cancers including OS. In this review, we discuss the mechanism of actions of MMPs in progression of OS, and the therapeutic use of MMPs inhibitors in the treatment of OS with subsequent clinical studies and future management. The expression of MMPs is upregulated in cancer cells by a variety of cytokines and growth factors, and upregulation of MMPs induces degradation of the extracellular matrix that contributes to cell proliferation by releasing growth factors. MMPs promote the detachment and migration of endothelial cells, cross the basement membrane as well as invade the surrounding lymphatic vessels and causes cancer metastasis. The use of selective MMP inhibitors with limited side effects might be promising therapeutic strategy in the treatment of OS. More clinical trials are necessary to evaluate the role of selective MMPs inhibitors in the prevention and treatment of OS along with their assessment of toxicity.

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EFEMP1 promotes the migration and invasion of osteosarcoma via MMP-2 with induction by AEG-1 via NF-κB signaling pathway

Cited by 54 publications

References 41 publications

Epidermal growth factor‐containing fibulin‐like extracellular matrix protein 1 (EFEMP1) suppressed the growth of hepatocellular carcinoma cells by promoting Semaphorin 3B(SEMA3B)

Epidermal growth factor‐containing fibulin‐like extracellular matrix protein 1 (EFEMP1) suppressed the growth of hepatocellular carcinoma cells by promoting Semaphorin 3B(SEMA3B)

Interaction with AEG-1 and MDM2 is associated with glioma development and progression and correlates with poor prognosis

Pathological and therapeutic aspects of matrix metalloproteinases: Implications in osteosarcoma

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