Astrocyte elevated gene-1 regulates CCL3/CCR5-induced epithelial-to-mesenchymal transition via Erk1/2 and Akt signaling in cardiac myxoma

Shi, Ping; Fang, Changcun; Pang, Xinyan

doi:10.3892/or.2015.4081

Cited by 14 publications

(11 citation statements)

References 28 publications

(29 reference statements)

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“…Additionally, AEG-1 performs its functions through mitogen-activated protein kinase, extracellular signal-regulated kinase, phosphatidylinositol 3-kinase/protein kinase B, and signal transducer and activator of transcription 3 signalling pathways. [40][41][42][43] These findings suggest that these signalling pathways may be also involved in the functions of AEG-1 in melanoma. In the present study, AEG-1 silencing was found to inhibit the growth of melanoma cells in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 82%

“…Consistently, in our study, the activation of the Wnt/β‐catenin signalling pathway was inhibited by AEG‐1 silencing, which indicates that AEG‐1 may exert its oncogenic role in melanoma cells through the Wnt/β‐catenin signalling pathway. Additionally, AEG‐1 performs its functions through mitogen‐activated protein kinase, extracellular signal‐regulated kinase, phosphatidylinositol 3‐kinase/protein kinase B, and signal transducer and activator of transcription 3 signalling pathways . These findings suggest that these signalling pathways may be also involved in the functions of AEG‐1 in melanoma.…”

Section: Discussionmentioning

confidence: 91%

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Silencing of astrocyte elevated gene‐1 inhibits proliferation and migration of melanoma cells and induces apoptosis

Zhang

Peng

Wang

et al. 2017

Clin Exp Pharma Physio

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Melanoma is an aggressive skin malignancy with a high mortality. Astrocyte elevated gene-1 (AEG-1), a downstream target of Ras and c-Myc, has been implicated in the development of multiple tumours, but its role in melanoma remains unclear. In the present study, the role of AEG-1 in melanoma was explored through AEG-1 silencing. Our results showed that silencing AEG-1 inhibited the proliferation of melanoma cells, induced cell cycle arrest, and reduced levels of cyclin A, cyclin B, cyclin D1, cyclin E, and cyclin-dependent kinase 2. AEG-1silencing also induced apoptosis in melanoma cells and altered the levels of cleaved caspase-3, B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein. Moreover, silencing AEG-1 suppressed the migration and invasion of melanoma cells, reduced the expressions and activities of matrix metallopeptidase (MMP)-2 and MMP-9, and inhibited the activation of the Wnt/β-catenin signalling pathway in melanoma cells. Furthermore, in vivo experiments revealed that AEG-1 silencing inhibited the growth of melanoma xenografts in nude mice. In summary, our study demonstrates an oncogenic role of AEG-1 in melanoma and suggests that AEG-1 may serve as a potential therapeutic target in the treatment of melanoma.

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Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 91%

Silencing of astrocyte elevated gene‐1 inhibits proliferation and migration of melanoma cells and induces apoptosis

Zhang

Peng

Wang

et al. 2017

Clin Exp Pharma Physio

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“…AEG-1 has been proven to exert functions in the development of various types of cancer, including liver cancer ( 19 , 29 ), breast cancer ( 30 ), colorectal cancer ( 18 , 31 ), lung cancer ( 32 ) and ovarian cancer ( 33 ). It has been reported that C-C motif chemokine 3/C-C chemokine receptor type 5-induced EMT may be regulated by AEG-1 via extracellular signal-regulated kinase 1/2 and RAC-α serine/threonine protein kinase signaling in cardiac myxoma ( 34 ). In addition, a study analyzed the role of miR-302c-3p in suppressing the invasion and proliferation of glioma cells by downregulating AEG-1 expression ( 15 ).…”

Section: Discussionmentioning

confidence: 99%

miR‑96 inhibits EMT by targeting AEG‑1 in glioblastoma cancer cells

et al. 2017

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The induction of epithelial to mesenchymal transition (EMT) is important for carcinogenesis and cancer progression. Previous studies have estimated that microRNA (miRNA/miR) expression is associated with EMT via the regulation of the expression of target genes. miR-96 has been reported to exhibit a correlation with the EMT process. However, the functional role of miR-96 and its mechanism in glioblastoma multiforme (GBM) remains to be completely elucidated. The objective of the present study was to investigate the functional role and mechanism of miR-96 in the migration and invasion, in addition to proliferation, apoptosis and cell cycle distribution, of GBM. In the present study, the results suggested that the introduction of miR-96 significantly inhibited the migration and invasion, in addition to proliferation and cell cycle progression, of GBM cells and promoted their apoptosis in vitro, leading to the hypothesis that miR-96 may be a potential tumor suppressor. It was subsequently confirmed that astrocyte elevated gene-1 (AEG-1) was a direct target gene of miR-96, using a luciferase assay and reverse transcription-quantitative polymerase chain reaction analysis, in addition to western blotting. miR-96 was observed to downregulate the expression of AEG-1 at the mRNA and protein levels. Notably, AEG-1 may suppress EMT by increasing the expression levels of E-cadherin, an epithelial marker, and decreasing the expression levels of vimentin, a mesenchymal marker. Therefore, it was concluded that miR-96 may impede the EMT process by downregulating AEG-1 in GBM. Additionally, it was observed that inhibition of AEG-1 led to a similar effect compared with overexpression of miR-96 in GBM. In conclusion, the results of the present study demonstrated that miR-96 may act as a tumor suppressor by regulating EMT via targeting of AEG-1, suggesting that miR-96 may be a potential biomarker and anticancer therapeutic target for GBM in the future.

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“…In recent years, many studies have established a positive correlation between AEG-1 expression and EMT status in cancer progression, including in lung cancer 29 , cardiac myxoma 30 , glioblastoma 31 and tongue squamous cell carcinoma (TSCC) 32 . In our study, we found increased expression of vimentin and decreased expression of E-cadherin in OSCC cell lines stably overexpressing AEG-1, which suggests that AEG-1 promotes EMT.…”

Section: Discussionmentioning

confidence: 99%

Astrocyte elevated gene-1 promotes tumour growth and invasion by inducing EMT in oral squamous cell carcinoma

Wang

Sun

et al. 2017

Sci Rep

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Oral squamous cell carcinoma (OSCC) is a common human malignancy with a high incidence rate and poor prognosis. Although astrocyte elevated gene 1 (AEG-1) expression is up-regulated in various human cancers and plays an important role in carcinogenesis and tumour progression, the impact of AEG-1 on the development and progression of OSCC remains unclear. Accordingly, this study aims to clarify the biological significance of AEG-1 in OSCC. We found AEG-1 to be overexpressed in OSCC tissues compared to normal oral mucosa. Knockdown or overexpression of AEG-1 in OSCC cell lines showed that AEG-1 is important for tumour growth, apoptosis, drug tolerance, and maintaining epithelial-mesenchymal transition (EMT)-mediated cell migration and invasion in vitro. Moreover, in a xenograft-mouse model generated by AEG-1-overexpressing SCC15 cells, we found that higher expression of AEG-1 promoted tumour growth, angiogenesis, and EMT in vivo. These findings provide mechanistic insight into the role of AEG-1 in regulating OSCC tumour growth, apoptosis, drug tolerance, and invasion, as well as AEG-1-induced activation of p38 and NF-κB signalling, suggesting that AEG-1 is an important prognostic factor and therapeutic target for OSCC.Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Each year, 1.6 million new cases of HNSCC are diagnosed, with half localized in the oral cavity (oral squamous cell carcinoma, OSCC), and 33,3000 deaths 1 . Indeed, OSCC is an important component of the worldwide cancer burden; despite radical surgery combined with radiation, chemotherapy and targeted therapy, OSCC has a 5-year survival rate of only approximately 50% 2 . The pathogenesis of OSCC is complex, involving many genes and pathways, though the mechanism of OSCC development remains unclear.Metastasis is dependent on unique mechanisms by which cancer cells escape from the primary tissue and spread to surrounding tissues. As part of the epithelial-mesenchymal transition (EMT), molecular reprogramming is a crucial step in the metastasis of most carcinomas 3 . During metastatic progression, EMT causes primary epithelial-like tumour cells to acquire invasive potential, including increased motility and mesenchymal characteristics, which results in dissemination from the original tumour and intravasation into the tumour vessel. EMT-driven cells circulating in the blood then redifferentiate into a primary status via the mesenchymal-epithelial transition (MET) during colonisation of and growth at distant metastatic sites 4,5 . Because of the important roles of EMT in the metastatic process, controlling EMT progression in tumours is thought to be a promising strategy to inhibit metastasis and prolong patient survival.Astrocyte elevated gene-1 (AEG-1), also known as metadherin (MTDH) or LYsine-RIch CEACAM1 co-isolated (LYRIC), is a 582-amino acid, type II transmembrane protein without any known functional domains. Recently, numerous reports have demonstrated that AEG-1 might play a pivotal role in the pathogenesis, ...

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Astrocyte elevated gene-1 regulates CCL3/CCR5-induced epithelial-to-mesenchymal transition via Erk1/2 and Akt signaling in cardiac myxoma

Cited by 14 publications

References 28 publications

Silencing of astrocyte elevated gene‐1 inhibits proliferation and migration of melanoma cells and induces apoptosis

Silencing of astrocyte elevated gene‐1 inhibits proliferation and migration of melanoma cells and induces apoptosis

miR‑96 inhibits EMT by targeting AEG‑1 in glioblastoma cancer cells

Astrocyte elevated gene-1 promotes tumour growth and invasion by inducing EMT in oral squamous cell carcinoma

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