AEG-1/MTDH/LYRIC, the Beginning

Lee, Seok‐Geun; Kang, Dong‐Chul; DeSalle, Rob; Sarkar, Devanand; Fisher, Paul B.

doi:10.1016/b978-0-12-401676-7.00001-2

Cited by 57 publications

(32 citation statements)

References 109 publications

(282 reference statements)

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“…Astrocyte elevated gene-1 (AEG-1) was first identified as an upregulated transcript in primary human fetal astrocytes infected with HIV-1 or treated with TNF-α and later characterized as a major oncogene highly upregulated in a broad array of cancers including GBM (8–10). Subsequently, using in vivo phage screening the mouse AEG-1 gene was cloned and named met adherin (MTDH) based on its pro-metastasis role in tumor cell homing to lung (11).…”

Section: Introductionmentioning

confidence: 99%

Astrocyte Elevated Gene-1 Interacts with Akt Isoform 2 to Control Glioma Growth, Survival, and Pathogenesis

Emdad

Bacolod

et al. 2014

Cancer Research

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The oncogene AEG-1 (MTDH) is highly expressed in glioblastoma multiforme (GBM) and many other types of cancer, where it activates multiple signaling pathways that drive proliferation, invasion, angiogenesis, chemoresistance, radioresistance and metastasis. AEG-1 activates the Akt signaling pathway and Akt and c-Myc are positive regulators of AEG-1 transcription, generating a positive feedback loop between AEG-1 and Akt in regulating tumorigenesis. Here we describe in GBM cells a direct interaction between an internal domain of AEG-1 and the PH domain of Akt2, a major driver in GBM. Expression and interaction of AEG-1 and Akt2 are elevated in GBM and contribute to tumor cell survival, proliferation and invasion. Clinically, in silico gene expression and immunohistochemical analyses of patient specimens showed that AEG-1 and Akt2 expression correlated with GBM progression and reduced patient survival. AEG-1-Akt2 interaction prolonged stabilization of Akt2 phosphorylation at S474, regulating downstream signaling cascades which enable cell proliferation and survival. Disrupting AEG-1-Akt2 interaction by competitive binding of the Akt2-PH domain led to reduced cell viability and invasion. When combined with AEG-1 silencing, conditional expression of Akt2-PH markedly increased survival in an orthotopic mouse model of human GBM. Our study uncovers a novel molecular mechanism by which AEG-1 augments glioma progression and offers a rationale to block AEG-1-Akt2 signaling function as a novel GBM treatment.

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Section: Introductionmentioning

confidence: 99%

Astrocyte Elevated Gene-1 Interacts with Akt Isoform 2 to Control Glioma Growth, Survival, and Pathogenesis

Emdad

Bacolod

et al. 2014

Cancer Research

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“…AEG- 1 was first identified using subtraction hybridization as an up-regulated gene in primary human fetal astrocytes infected with HIV-1 (6, 7). Subsequent studies identified AEG- 1 as a metastasis-associated gene in the mouse, called metadherin (MTDH) (8), and as a lysine-rich CEACAM1 co-isolated gene in the rat, called LYRIC (9).…”

Section: Introductionmentioning

confidence: 99%

AEG-1 Promoter–Mediated Imaging of Prostate Cancer

et al. 2014

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We describe a new imaging method for detecting prostate cancer, whether localized or disseminated and metastatic to soft tissues and bone. The method relies on the use of imaging reporter genes under the control of the promoter of AEG-1 (MTDH), which is selectively active only in malignant cells. Through systemic, nanoparticle-based delivery of the imaging construct, lesions can be identified through bioluminescence imaging and single photon emission-computed tomography in the PC3-ML murine model of prostate cancer at high sensitivity. This approach is applicable for the detection of prostate cancer metastases, including bone lesions for which there is no current reliable agent for non-invasive clinical imaging. Further, the approach compares favorably to accepted and emerging clinical standards, including positron emission tomography with [18F]fluorodeoxyglucose and [18F]sodium fluoride. Our results offer a preclinical proof of concept that rationalizes clinical evaluation in patients with advanced prostate cancer.

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“…Several authors have implied that an up-regulation of AEG-1 enhances characteristics of malignant aggressiveness making it an independent prognostic factor for unfavourable clinical outcome. This suggests that AEG-1 is valuable as a prognostic biomarker of disease progression and survival in patients with EC [16][17][18].…”

Section: Biomarkers With Diagnostic Prognostic and Therapeutic Valuementioning

confidence: 96%

“…AEG-1 is located at chromosome 8q22 [15] and is also known as metadherin (MTDH) and lysine-rich CEACAM1 coisolated (LYRIC) [17]. Since its discovery in 2002, as HIV-and TNF--α-inducible gene in primary human fetal astrocytes [15], several authors have described its tumor-promoting activity which is related to the activation of diverse signal transduction pathways (PI3K/ AKT, NF-κB, MEK/ERK, WNT/β-catenin) involved in cancer progression, in addition to its role in pathogenesis, metastasis, invasion, angiogenesis and overall patient survival [16]. It should be noticed that AEG-1 is an important oncogene were its expression status is firmly established in a subsequent array of cancers.…”

Section: Biomarkers With Diagnostic Prognostic and Therapeutic Valuementioning

confidence: 99%

Biological markers with potential clinical value in endometrial cancer — review of the literature

et al. 2017

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Endometrial carcinoma (EC) is the most common malignancy of the female genital tract encountered in western countries, making it the fourth most common cancer in women. The incidence of uterine cancer is on the rise throughout the developed world where diagnosis is increasingly observed among younger patients. With regard to this, attention has been focused on conducting more studies to achieve a better understanding of the molecular genetics related to endometrial carcinogenesis. Over the years, EC has been classified into two broad histopathological subtypes based on the mechanism of development, and we can therefore observe specific biomarkers related to the respective subtype. Based on this idea, more research has been carried out in the last decade, using biotechnological methods, with the aim to identify new potential tumor markers. By translating these findings into clinical use one may facilitate accurate diagnosis and prognostic prediction, and contribute to individualized treatment. Without a doubt, there is a demanding need to identify biomarkers that can be adopted in clinical practice in order to reduce the time needed to obtain diagnosis. Such markers may be of great value in improving patient outcome. However, a number of problems remain to be solved before this becomes a reality. This paper briefly reviews the current status of rising biomarkers in EC.

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AEG-1/MTDH/LYRIC, the Beginning

Cited by 57 publications

References 109 publications

Astrocyte Elevated Gene-1 Interacts with Akt Isoform 2 to Control Glioma Growth, Survival, and Pathogenesis

Astrocyte Elevated Gene-1 Interacts with Akt Isoform 2 to Control Glioma Growth, Survival, and Pathogenesis

AEG-1 Promoter–Mediated Imaging of Prostate Cancer

Biological markers with potential clinical value in endometrial cancer — review of the literature

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