EphrinA5 acts as a tumor suppressor in glioma by negative regulation of epidermal growth factor receptor

Jj, Li; Dp, Liu; Gt, Liu; Xie, Dong

doi:10.1038/onc.2009.15

Cited by 61 publications

(59 citation statements)

References 36 publications

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“…Ephrin-B2 has also been implicated in the advancement of uterine endometrial, ovarian and cervical cancers [41,43,44]. By contrast, forced expression of ephrin-A5 suppressed tumor formation by U373 glioma cells through negative regulation of EGFR [34], while elevated expression of both ephrin-B2 and ephrin-B3 has been associated with suppression of the malignant phenotype of neuroblastoma [45,46].…”

Section: Tumorigenicitymentioning

confidence: 90%

“…Glioma RT-PCR ↓ Expression in GBM tissue (n = 23) compared with normal tissue (n = 5) [34] Ovarian Ephrin-A1, A4, B1 and B2 have been detected in vascular endothelium in a range of cancers, including breast, osteosarcoma, Kaposi's sarcoma and urinary bladder carcinoma, especially at the sites of tumor neovascularization [32,[61][62][63][64]. Furthermore, it has been demonstrated that activation of endothelial ephrin-B1 promoted neovascularization [65].…”

Section: Ephrin-a1mentioning

confidence: 98%

“…Aberrant ephrin expression has been associated with many human malignancies, including various carcinomas, melanoma, sarcoma and brain tumors [30][31][32][33][34]. Their role in cancer is not yet understood as some tumors present with elevated levels of ephrin expression, while others demonstrate decreased expression.…”

Section: Ephrin Expression In Cancermentioning

confidence: 99%

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Ephrin Expression and Function in Cancer

et al. 2009

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Ephrins are cell membrane-associated signaling proteins bound by transmembrane Eph receptors on juxtaposed cells. Eph-ephrin interactions result in bidirectional signaling within both receptor- and ligand-bearing cells, with diverse consequences for cell morphology and behavior. Such interactions are especially important during early vertebrate development, and growing evidence has revealed equally important roles in adult-tissue homeostasis. As for the Eph receptors, abnormal expression of ephrins is associated with disease, especially cancer. The ephrins have received less attention than the Ephs in the literature, owing, in part, to their later discovery and that they are fewer in number. Here, we attempt to redress this imbalance and provide an 'ephrin-centric' discussion of the expression and function of ephrins in cancer.

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Section: Tumorigenicitymentioning

confidence: 90%

Section: Ephrin-a1mentioning

confidence: 98%

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Ephrin Expression and Function in Cancer

et al. 2009

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“…GLT1 and GLAST colocalize with ephrin-A3 on astrocyte processes, suggesting a functional crosstalk between these proteins that may depend on their physical proximity . Further studies are needed to determine if ephrin-A3 reverse signaling regulates glutamate transporters through activation of Src kinases and/or by ubiquitination and degradation (Baba et al, 2009;Davy and Robbins, 2000;Davy et al, 1999;Holen et al, 2008;Huai and Drescher, 2001;Li et al, 2009). A better understanding of ephrin-A3 reverse signaling pathways in astrocytes will likely provide important insight into the mechanisms regulating extracellular glutamate levels in the hippocampus.…”

Section: Ephrin-a3 Reverse Signaling In Astrocytesmentioning

confidence: 96%

Eph receptors and ephrins in neuron–astrocyte communication at synapses

Murai

Pasquale

2011

Glia

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Neuron-glia communication is essential for regulating the properties of synaptic connections in the brain. Astrocytes, in particular, play a critical and complex role in synapse development, maintenance, and plasticity. Likewise, neurons reciprocally influence astrocyte physiology. However, the molecular signaling events that enable astrocytes and neurons to effectively communicate with each other are only partially defined. Recent findings have revealed that Eph receptor tyrosine kinases and ephrins play an important role in contact-dependent neuron-glia communication at synapses. Upon binding, these two families of cell surface-associated proteins trigger bidirectional signaling events that regulate the structural and physiological properties of both neurons and astrocytes. This review will focus on the emerging role of Eph receptors and ephrins in neuron-astrocyte interaction at synapses and discuss implications for synaptic plasticity, behavior, and disease.

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“…Interestingly, they have been assigned both tumor promoter and suppressor functions in different cellular contexts [14][15][16][17][18][19]. As mentioned earlier, many of the functions regulated by Eph/Ephrin signaling are cell guidance functions directly reminiscent of the metastatic process.…”

Section: Introductionmentioning

confidence: 95%

The Eph/Ephrin family in cancer metastasis: communication at the service of invasion

Kandouz

2012

Cancer Metastasis Rev

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Cancer cells rely on intercellular communication throughout the different stages of their transformation and progression into metastasis. They do so by co-opting different processes such as cell-cell junctions, growth factors, receptors, and vesicular release. Initially characterized in neuronal and vascular tissues, Ephs and Ephrins, the largest family of receptor tyrosine kinases, comprised of two classes (i.e., A and B types), is increasingly scrutinized by cancer researchers. These proteins possess the particular features of both the receptors and ligands being membrane-bound which, via mandatory direct cell-cell interactions, undergo a bidirectional signal transduction initiated from both the receptor and the ligand. Following cell-cell interactions, Ephs/Ephrins behave as guidance molecules which trigger both repulsive and attractive signals, so as to direct the movement of cells through their immediate microenvironment. They also direct processes which include sorting and positioning and cytoskeleton rearrangements, thus making them perfect candidates for the control of the metastatic process. In fact, the role of Ephs and Ephrins in cancer progression has been demonstrated for many of the family members and they, surprisingly, have both tumor promoter and suppressor functions in different cellular contexts. They are also able to coordinate between multiple processes including cell survival, proliferation, differentiation, adhesion, motility, and invasion. This review is an attempt to summarize the data available on these Ephs/Ephrins' biological functions which contribute to the onset of aggressive cancers. I will also provide an overview of the factors which could explain the functional differences demonstrated by Ephs and Ephrins at different stages of tumor progression and whose elucidation is warranted for any future therapeutic targeting of this signaling pathway in cancer metastasis.

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EphrinA5 acts as a tumor suppressor in glioma by negative regulation of epidermal growth factor receptor

Cited by 61 publications

References 36 publications

Ephrin Expression and Function in Cancer

Ephrin Expression and Function in Cancer

Eph receptors and ephrins in neuron–astrocyte communication at synapses

The Eph/Ephrin family in cancer metastasis: communication at the service of invasion

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