Aeg-1/MTDH/Lyric

Sarkar, Devanand; Fisher, Paul B.

doi:10.1016/b978-0-12-401676-7.00002-4

Cited by 76 publications

(51 citation statements)

References 82 publications

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“…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). Recent studies in multiple cancers confirm a significant role for AEG- 1 as an oncogene (10) implicated in cancer development and progression in many organ sites (11). Based on the diverse roles of AEG- 1 in tumor progression, including transformation, growth regulation, cell survival, prevention of apoptosis, cell migration and invasion, metastasis, angiogenesis, and resistance to chemotherapy (12), this gene may provide a viable target for developing therapies for diverse cancers.…”

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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Section: Introductionmentioning

confidence: 99%

AEG-1 Promoter–Mediated Imaging of Prostate Cancer

et al. 2014

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“…Astrocyte Elevated Gene-1 (AEG-1), also known as Metadherin (MTDH) and LYRIC, is an oncogene that is overexpressed in all cancers (21). AEG-1 overexpression is detected with the progression of cancer, especially in the aggressive metastatic stage, and negatively correlates with poor survival and overall adverse prognosis (21).…”

Section: Introductionmentioning

confidence: 99%

“…AEG-1 overexpression is detected with the progression of cancer, especially in the aggressive metastatic stage, and negatively correlates with poor survival and overall adverse prognosis (21). In vitro studies and investigations using nude mice xenograft and metastatic models with diverse cancer cell lines documented that AEG-1 overexpression induces an aggressive, angiogenic and metastatic phenotype whereas knockdown of AEG-1 inhibits proliferation and invasion and markedly abrogates tumor growth and metastasis (22–25).…”

Section: Introductionmentioning

confidence: 99%

Genetic Deletion of AEG-1 Prevents Hepatocarcinogenesis

et al. 2014

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Activation of the oncogene AEG-1 (MTDH, LYRIC) has been implicated recently in the development of hepatocellular carcinoma (HCC). In mice, HCC can be initiated by exposure to the carcinogen DEN, which has been shown to rely upon activation of NF-κB in liver macrophages. Since AEG-1 is an essential component of NF-κB activation, we interrogated the susceptibility of mice lacking the AEG-1 gene to DEN-induced hepatocarcinogenesis. AEG-1-deficient mice displayed resistance to DEN-induced HCC and lung metastasis. No difference was observed in the response to growth factor signaling or activation of Akt, ERK and β-catenin, compared to wild-type control animals. However, AEG-1-deficient hepatocytes and macrophages exhibited a relative defect in NF-κB activation. Mechanistic investigations showed that IL-6 production and STAT-3 activation, two key mediators of HCC development, were also deficient along with other biological and epigenetics findings in the tumor microenvironment confirming that AEG-1 supports an NF-κB-mediated inflammatory state that drives HCC development. Overall, our findings offer in vivo proofs that AEG-1 is essential for NF-κB activation and hepatocarcinogenesis, and they reveal new roles for AEG-1 in shaping the tumor microenvironment for HCC development.

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“…In recent years, elevated levels of MTDH have been reported in more than 20 cancer types (4), suggesting a potentially crucial and broad functionality of this gene in human cancer. Depending on the cancer type tested, recent studies using mainly cell culture systems have implicated MTDH in many cancer-related processes, including cellular proliferation, stress-induced cell death, invasion, chemoresistance and metastasis (5, 6).…”

Section: Introductionmentioning

confidence: 99%

Genetic Ablation of Metadherin Inhibits Autochthonous Prostate Cancer Progression and Metastasis

Wan

Wei

et al. 2014

Cancer Research

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Metadherin (MTDH) overexpression in diverse cancer types has been linked to poor clinical outcomes, but definitive genetic proof of its contributions to cancer remain incomplete. In particular, the degree to which MTDH may contribute to malignant progression in vivo is lacking. Here, we report that MTDH is amplified frequently in human prostate cancers where its expression levels are tightly correlated with prostate cancer progression and poor disease-free survival. Further, we show that genetic ablation of MTDH in the TRAMP transgenic mouse model of prostate cancer blocks malignant progression without causing defects in the normal development of the prostate. Germline deletion of Mtdh in TRAMP mice prolonged tumor latency, reduced tumor burden, arrested progression of prostate cancer at well-differentiated stages and inhibited systemic metastasis to distant organs, thereby decreasing cancer-related mortality ~10-fold. Consistent with these findings, direct silencing of Mtdh in prostate cancer cells decreased proliferation in vitro and tumor growth in vivo, supporting an epithelial cell-intrinsic role of MTDH in prostate cancer. Together, our findings establish a pivotal role for MTDH in prostate cancer progression and metastasis and define MTDH as a therapeutic target in this setting.

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Aeg-1/MTDH/Lyric

Cited by 76 publications

References 82 publications

AEG-1 Promoter–Mediated Imaging of Prostate Cancer

AEG-1 Promoter–Mediated Imaging of Prostate Cancer

Genetic Deletion of AEG-1 Prevents Hepatocarcinogenesis

Genetic Ablation of Metadherin Inhibits Autochthonous Prostate Cancer Progression and Metastasis

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