Astrocyte elevated gene-1 (AEG-1) functions as an oncogene and regulates angiogenesis

Emdad, Luni; Lee, Seok-Geun; Su, Zhao Zhong; Jeon, Hyun Yong; Boukerche, Habib; Sarkar, Devanand; Fisher, Paul B.

doi:10.1073/pnas.0910936106

Cited by 181 publications

(214 citation statements)

References 52 publications

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“…Taken together, our results indicate that AEG-1 may play important roles in the pathogenesis of RCC. An increasing evidence shows that AEG-1-expressing tumors have increased microvessel density ( MVD) and overexpression of it promotes angiogenesis both in vitro and in vivo which suggests AEG-1 plays a dominant positive role in angiogenesis thus contribute to tumor metastasis [14].In this study, we have shown that both the mRNA and protein levels of AEG-1 were markedly higher in RCC cell lines than those in human normal tubular epithelial cell HK-2. It is very interesting that in ACHN and OS-RC-2 cell lines, which show epithelial-like phenotype, real-time PCR analysis have shown only about 2-fold increase of AEG-1 message.…”

Section: Discussionmentioning

confidence: 62%

“…Statistical analysis suggests that it is possible to use AEG-1 as a clinically relevant indicator for disease progression and predictor for patient survival. The PI3K/Akt pathway has a pivotal role in renal cell carcinoma pathogenesis [18] and contribute centrally to the AEG-1 induced angiogenesis [14], thus, AEG-1 may represents an ideal target for therapeutic intervention against RCC. For this purpose, further investigations clarifying its role and the mechanism in carcinogenesis and progression by functional analysis are needed.…”

Section: Discussionmentioning

confidence: 99%

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Overexpression of AEG-1 in renal cell carcinoma and its correlation with tumor nuclear grade and progression

Chen¹,

Z²,

H³

et al. 2010

neo

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The study was aimed at detecting the expression of a newly found oncogene, astrocyte elevated gene-1 (AEG-1), in renal cell carcinoma (RCC) and its correlation with histopathologic features and the survival of patients. Real-time reverse transcription-PCR and Western blot showed markedly higher expression of AEG-1 in 8 cases of RCC tissue compared with the paired normal tissue from the same patient. The expression level of AEG-1 was also increased in four RCC cell lines in contrast with normal tubular epithelial human kidney cells 2 (HK-2) at both mRNA and protein levels. Furthermore, immunohistochemistry analysis showed highly expressed AEG-1 in 96 of 102 (94.1%) cases of paraffin-embedded archival RCC tissue. Statistical analysis showed a significant correlation of AEG-1 expression with tumor grade (P <0.001), clinical staging (P = 0.003), T classification (P = 0.003) as well as metastasis classification (P=0.032). The means for survival time of low AEG-1 expression group was 76.98m while high AEG-1expression group was 60.94m. Our results suggest that AEG-1 protein is overexpressed in RCC and plays an important role in tumor differentiation and progression. High AEG-1 expression is closely associated with poor prognosis.

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Section: Discussionmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Overexpression of AEG-1 in renal cell carcinoma and its correlation with tumor nuclear grade and progression

Chen¹,

Z²,

H³

et al. 2010

neo

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“…Recently, clinical studies have revealed that MTDH is overexpressed in various malignancies, including breast, prostate, glioma, hepatocellular, and esophageal cancer and is associated with disease progression and poor clinical outcomes (14). Moreover, MTDH has been found to promote cancer metastasis, chemoresistance, invasion and angiogenesis (15)(16)(17)(18)(19)(20)(21), suggesting that it may function as an oncogene. Furthermore, MTDH knockdown has been found to sensitize breast cancer and neuroblastoma cells to cisplatin (15,17).…”

Section: Introductionmentioning

confidence: 99%

Metadherin regulates radioresistance in cervical cancer cells

et al. 2012

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Abstract. Metadherin (MTDH) promotes cancer metastasis, chemoresistance, invasion and angiogenesis. Upregulation of MTDH is correlated with both progression and poor clinical outcome of many types of cancers; however, there is currently no information regarding the role of MTDH in radiation sensitivity. Here, we investigated the effects of MTDH on the radiosensitivity of cervical cancer cells using the SiHa cell line. We discovered that cervical cancer cells in which MTDH was knocked down had significantly increased radiosensitivity as measured by a clonogenic assay. MTDH knockdown cells also had increased apoptosis and a decreased proportion of cells arrested in the G2 phase after radiation treatment. MTDH knockdown also weakened the repair of DNA double-strand breaks (DSBs) induced by radiation. These results indicate that MTDH affects the radiosensitivity of cervical cancer cells and that MTDH may be a novel target to improve cervical cancer radiation response.

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“…MTDH has been shown to be a key functional target of the 8q22 genomic gain that is frequently observed in poor prognosis breast cancer patients (6). Beyond promoting experimental lung metastasis (3, 6), multiple studies have implicated MTDH as a mediator of several cancer-related processes, such as oncogenesis and angiogenesis (7,8), invasion (9), chemoresistance (6, 10 -12), apoptosis resistance (13), and autophagy (14). Despite the abundance of MTDH phenotypes, a consensus understanding of its underlying molecular mechanisms has not yet been reached.…”

mentioning

confidence: 99%

Identification of Staphylococcal Nuclease Domain-containing 1 (SND1) as a Metadherin-interacting Protein with Metastasis-promoting Functions

Blanco

Alečković

Hua

et al. 2011

Journal of Biological Chemistry

114

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Metastasis is the deadliest and most poorly understood feature of malignant diseases. Recent work has shown that Metadherin (MTDH) is overexpressed in over 40% of breast cancer patients and promotes metastasis and chemoresistance in experimental models of breast cancer progression. Here we applied mass spectrometry-based screen to identify staphylococcal nuclease domain-containing 1 (SND1) as a candidate MTDH-interacting protein. After confirming the interaction between SND1 and MTDH, we tested the role of SND1 in breast cancer and found that it strongly promotes lung metastasis. SND1 was further shown to promote resistance to apoptosis and to regulate the expression of genes associated with metastasis and chemoresistance. Analyses of breast cancer clinical microarray data indicated that high expression of SND1 in primary tumors is strongly associated with reduced metastasis-free survival in multiple large scale data sets. Thus, we have uncovered SND1 as a novel MTDH-interacting protein and shown that it is a functionally and clinically significant mediator of metastasis.Metastasis is responsible for the majority of cancer-related deaths (1). An increasing number of genes have been implicated in mediating different steps of metastasis, but relatively few are mechanistically well characterized (2). One recently verified mediator of distant metastasis is Metadherin (MTDH 3 ; also called Lyric and AEG1 (3-5)). MTDH has been shown to be a key functional target of the 8q22 genomic gain that is frequently observed in poor prognosis breast cancer patients (6). Beyond promoting experimental lung metastasis (3, 6), multiple studies have implicated MTDH as a mediator of several cancer-related processes, such as oncogenesis and angiogenesis (7,8), invasion (9), chemoresistance (6, 10 -12), apoptosis resistance (13), and autophagy (14). Despite the abundance of MTDH phenotypes, a consensus understanding of its underlying molecular mechanisms has not yet been reached. MTDH has been shown to influence several oncogenic signaling pathways and transcription factors, such as Ha-Ras (15), PI3K/AKT (13), ERK, Wnt/␤-catenin (8), NF-B (16), c-Myc (15), and FOXO1/FOXO3a (17, 18). However, MTDH regulation of signaling pathways appears to be context-dependent with affected pathways varying by tumor type and cell line (19,20). Furthermore, prior work on MTDH molecular mechanisms has largely focused on hypothesis-driven investigations into the ability of MTDH to influence classical oncogenic pathways with little exploration to date on protein-level interactions (16,21).In this study, we aimed to expand the knowledge of MTDH molecular functionality and also uncover novel genes involved in promoting distant metastasis. Our approach utilized an unbiased, mass spectrometry-based screen for MTDH-interacting partners. We identified and characterized the interaction between MTDH and one such protein, SND1. SND1 is a multifunctional protein with reported roles in transcriptional activation (22), RNA editing (23, 24), formation of the RNAinduced ...

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Astrocyte elevated gene-1 (AEG-1) functions as an oncogene and regulates angiogenesis

Abstract: angiogenesis-related molecules ͉ tumor progression

Cited by 181 publications

References 52 publications

Overexpression of AEG-1 in renal cell carcinoma and its correlation with tumor nuclear grade and progression

Overexpression of AEG-1 in renal cell carcinoma and its correlation with tumor nuclear grade and progression

Metadherin regulates radioresistance in cervical cancer cells

Identification of Staphylococcal Nuclease Domain-containing 1 (SND1) as a Metadherin-interacting Protein with Metastasis-promoting Functions

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