Dlxin-1, a member of MAGE family, inhibits cell proliferation, invasion and tumorigenicity of glioma stem cells

Emani, Maheswarareddy; Chettiar, Sivarajan T.; Kaur, Navjot; Ganeshkumar, R; Shepal, Varsha; Shanbhag, Nagesh C; Shiras, Anjali

doi:10.1038/cgt.2010.71

Cited by 20 publications

(11 citation statements)

References 36 publications

(48 reference statements)

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“…During the past decade, emerging evidence supports the notion that CSCs are responsible for tumor development including tumor initiation, invasion, angiogenesis, therapy resistance, and recurrence [33]–[35]. GSCs have been demonstrated to be highly invasive [36], [37]. In fact, invasive glioma cells show tumor stem cell characteristics with neurosphere formation ability and tumorigenicity [34], [38].…”

Section: Discussionmentioning

confidence: 99%

A Novel Zebrafish Xenotransplantation Model for Study of Glioma Stem Cell Invasion

et al. 2013

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Invasion and metastasis of solid tumors are the major causes of death in cancer patients. Cancer stem cells (CSCs) constitute a small fraction of tumor cell population, but play a critical role in tumor invasion and metastasis. The xenograft of tumor cells in immunodeficient mice is one of commonly used in vivo models to study the invasion and metastasis of cancer cells. However, this model is time-consuming and labor intensive. Zebrafish (Danio rerio) and their transparent embryos are emerging as a promising xenograft tumor model system for studies of tumor invasion. In this study, we established a tumor invasion model by using zebrafish embryo xenografted with human glioblastoma cell line U87 and its derived cancer stem cells (CSCs). We found that CSCs-enriched from U87 cells spreaded via the vessels within zebrafish embryos and such cells displayed an extremely high level of invasiveness which was associated with the up-regulated MMP-9 by CSCs. The invasion of glioma CSCs (GSCs) in zebrafish embryos was markedly inhibited by an MMP-9 inhibitor. Thus, our zebrafish embryo model is considered a cost-effective approach tostudies of the mechanisms underlying the invasion of CSCs and suitable for high-throughput screening of novel anti-tumor invasion/metastasis agents.

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Section: Discussionmentioning

confidence: 99%

A Novel Zebrafish Xenotransplantation Model for Study of Glioma Stem Cell Invasion

et al. 2013

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“…This includes the MAGE family of proteins that bind to specific E3 RING ubiquitin ligases and form stable complexes referred to as MAGE-RING ligases (MRLs). A number of proteomic studies have identified many MRLs, including those involving both type I and II MAGEs (including MAGE-A1, -A2, -A3, -A6, -B2, -B18, -C2, -D1, -E1, -F1, -G1, -L2 and NECDIN) that bind to specific E3 RING ligases (including, LNX1, NSE1, PRAJA1, RBX1, TRIM27, TRIM28, and TRIM31) (18, 26, 30-32). MAGEs bind E3 ligases through their MHD that is both necessary and sufficient for binding (18).…”

Section: Mage-ring Ligases (Mrls)mentioning

confidence: 99%

Cellular and disease functions of the Prader–Willi Syndrome geneMAGEL2

Tacer

Potts

2017

Biochemical Journal

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Melanoma antigen L2 (MAGEL2 or MAGE-L2) is a member of the MAGE family of ubiquitin ligase regulators. It is maternally imprinted and often paternally deleted or mutated in the related neurodevelopmental syndromes, Prader-Willi Syndrome (PWS) and Schaaf-Yang Syndrome (SHFYNG). MAGEL2 is highly expressed in the hypothalamus and plays an important role in a fundamental cellular process that recycles membrane proteins from endosomes through the retromer sorting pathway. MAGEL2 is part of a multi-subunit protein complex consisting of MAGEL2, the TRIM27 E3 ubiquitin ligase, and the USP7 deubiquitinating enzyme. The MAGEL2-USP7-TRIM27 (or MUST) complex facilitates the retromer recycling pathway through ubiquitination and activation of the WASH actin nucleation promoting factor. This review provides an overview of the MAGE protein family of ubiquitin ligases regulators and details the molecular and cellular role of MAGEL2 in ubiquitination, actin regulation, and endosomal sorting processes, as well as MAGEL2 implications in PWS and SHFYNG disorders and its physiological functions elucidated through the study of Magel2 knockout mouse models.

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“…During the past decade, emerging evidence supports the notion that cancer stem cells (CSCs) or cancer-initiating cells are responsible for tumor development including invasion and angiogenesis, therapy resistance, and recurrence (3)(4)(5)(6). Glioma stem-like cells (GSLCs) have been demonstrated to possess highly invasive activity (7,8). Besides, the invasive glioma cells present stem cell characteristics with increasing neurosphere formation ability and tumorigenicity (4,9).…”

mentioning

confidence: 99%

Tumor-Associated Microglia/Macrophages Enhance the Invasion of Glioma Stem-like Cells via TGF-β1 Signaling Pathway

Xin

et al. 2012

The Journal of Immunology

418

309

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The invasion of malignant glioma cells into the surrounding normal brain tissues is crucial for causing the poor outcome of this tumor type. Recent studies suggest that glioma stem-like cells (GSLCs) mediate tumor invasion. However, it is not clear whether microenvironment factors, such as tumor-associated microglia/macrophages (TAM/Ms), also play important roles in promoting GSLC invasion. In this study, we found that in primary human gliomas and orthotopical transplanted syngeneic glioma, the number of TAM/Ms at the invasive front was correlated with the presence of CD133(+) GSLCs, and these TAM/Ms produced high levels of TGF-β1. CD133(+) GSLCs isolated from murine transplanted gliomas exhibited higher invasive potential after being cocultured with TAM/Ms, and the invasiveness was inhibited by neutralization of TGF-β1. We also found that human glioma-derived CD133(+) GSLCs became more invasive upon treatment with TGF-β1. In addition, compared with CD133(-) committed tumor cells, CD133(+) GSLCs expressed higher levels of type II TGF-β receptor (TGFBR2) mRNA and protein, and downregulation of TGFBR2 with short hairpin RNA inhibited the invasiveness of GSLCs. Mechanism studies revealed that TGF-β1 released by TAM/Ms promoted the expression of MMP-9 by GSLCs, and TGFBR2 knockdown reduced the invasiveness of these cells in vivo. These results demonstrate that TAM/Ms enhance the invasiveness of CD133(+) GSLCs via the release of TGF-β1, which increases the production of MMP-9 by GSLCs. Therefore, the TGF-β1 signaling pathway is a potential therapeutic target for limiting the invasiveness of GSLCs.

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Dlxin-1, a member of MAGE family, inhibits cell proliferation, invasion and tumorigenicity of glioma stem cells

Cited by 20 publications

References 36 publications

A Novel Zebrafish Xenotransplantation Model for Study of Glioma Stem Cell Invasion

A Novel Zebrafish Xenotransplantation Model for Study of Glioma Stem Cell Invasion

Cellular and disease functions of the Prader–Willi Syndrome geneMAGEL2

Tumor-Associated Microglia/Macrophages Enhance the Invasion of Glioma Stem-like Cells via TGF-β1 Signaling Pathway

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