Astrocyte Elevated Gene-1: A Novel Target for Human Glioma Therapy

Emdad, Luni; Sarkar, Devanand; Lee, Seok-Geun; Su, Zhao Zhong; Yoo, Byoung Kwon; Dash, Rupesh; Yacoub, Adly; Fuller, Christine; Shah, Khalid; Dent, Paul; Bruce, Jeffrey N.; Fisher, Paul B.

doi:10.1158/1535-7163.mct-09-0752

Cited by 98 publications

(114 citation statements)

References 37 publications

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“…This protein is frequently overexpressed in human brain tumors (Emdad et al, 2007). Gene expression and protein levels were elevated in several human brain tumors including malignant gliomas and suppression of AEG-1 activity diminished brain tumor growth in mice (Emdad et al, 2010). Reports suggest that the effects of AEG-1 on brain tumor invasion and metastasis involve the activities of MMP-2 and MMP-9 (Emdad et al, 2010;Liu et al, 2010).…”

Section: Astrocytes In the Microenvironment Of Brain Tumorsmentioning

confidence: 99%

The brain tumor microenvironment

Charles

Holland

Gilbertson

et al. 2011

Glia

681

317

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High-grade brain tumors are heterogeneous with respect to the composition of bona fide tumor cells and with respect to a range of intermingling parenchymal cells. Glioblastomas harbor multiple cell types, some with increased tumorigenicity and stem cell-like capacity. The stem-like cells may be the cells of origin for tumor relapse. However, the tumor-associated parenchymal cells such as vascular cells, microglia, peripheral immune cells, and neural precursor cells also play a vital role in controlling the course of pathology. In this review, we describe the multiple interactions of bulk glioma cells and glioma stem cells with parenchymal cell populations and highlight the pathological impact as well as signaling pathways known for these types of cell-cell communication. The tumor-vasculature not only nourishes glioblastomas, but also provides a specialized niche for these stem-like cells. In addition, microglial cells, which can contribute up to 30% of a brain tumor mass, play a role in glioblastoma cell invasion. Moreover, non-neoplastic astrocytes can be converted into a reactive phenotype by the glioma microenvironment and can then secrete a number of factors which influences tumor biology. The young brain may have the capacity to inhibit gliomagenesis by the endogenous neural precursor cells, which secrete tumor suppressive factors. The factors, pathways, and interactions described in this review provide a new prospective on the cell biology of primary brain tumors, which may ultimately generate new treatment modalities. However, our picture of the multiple interactions between parenchymal and tumor cells is still incomplete. V

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Section: Astrocytes In the Microenvironment Of Brain Tumorsmentioning

confidence: 99%

The brain tumor microenvironment

Charles

Holland

Gilbertson

et al. 2011

Glia

681

317

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show abstract

“…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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“…It is very clear now that AEG-1 is far more than just a gene regulated in astrocytes which contributes centrally to human gliomas. Numerous studies confirmed that it is also over-expressed in various human cancers including breast, lung, prostate, glioblastoma multiform and esophageal cancer [6][7][8][9][10]. AEG-1 plays an important role in PI3K/Akt signaling pathway and nuclear factor κ-B signaling pathway which regulate fundamental cellular functions, including proliferation, growth and survival, thus have critical function in cancer cell migration and invasion [11,12].…”

mentioning

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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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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Astrocyte Elevated Gene-1: A Novel Target for Human Glioma Therapy

Cited by 98 publications

References 37 publications

The brain tumor microenvironment

The brain tumor microenvironment

Metadherin regulates radioresistance in cervical cancer cells

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

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