<i>De novo</i> expression of EphA2 in osteosarcoma modulates activation of the mitogenic signalling pathway

Fritsche‐Guenther, Raphaela; Noske, Aurelia; Ungethüm, Ute; Kuban, Ralf‐Jürgen; Schlag, Peter M.; Tunn, Per‐Ulf; Karle, Janine; Krenn, Veit; Dietel, Manfred; Sers, Christine

doi:10.1111/j.1365-2559.2010.03713.x

Cited by 61 publications

(74 citation statements)

References 33 publications

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“…5E) (28). In addition, administration of eA1-Fc, eA1-WT, or the four mutants CM led to decreased migration of GBM cells, in line with the result obtained in breast and prostate cancer cells (37,44) and in contrast with data obtained in osteosarcoma (45).…”

Section: Discussionsupporting

confidence: 85%

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Structural and Functional Characterization of Monomeric EphrinA1 Binding Site to EphA2 Receptor

Tomé

Palma

Ferluga

et al. 2012

Journal of Biological Chemistry

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Section: Discussionsupporting

confidence: 85%

“…In contrast, other reports indicate that ERK1/2 activity is actually increased after treatment with eA1-Fc (44,45). The treatment of U-251 MG cells with eA1-P113A, -T115A, -G117A, and -E122A CM decreased phosphorylation of extracellular signal-regulated kinase beyond to what was seen with eA1-WT CM.…”

Section: Discussioncontrasting

confidence: 63%

Structural and Functional Characterization of Monomeric EphrinA1 Binding Site to EphA2 Receptor

Tomé

Palma

Ferluga

et al. 2012

Journal of Biological Chemistry

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“…Ephrin-A1 ligand binding induces increased EphA2 tyrosine phosphorylation and degradation, and downstream MAPK activation. In return, the MAPK pathway regulates Ephrin-A1 expression [117]. Activation of the fibroblast growth factor receptor (FGFR1) induces the phosphorylation of EphB2 in the absence of ligand stimulation.…”

Section: Phosphorylation and Kinase-dependence Of Eph/ephrin Signalinmentioning

confidence: 99%

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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“…The gene expression profile of GSE14359 [15] was downloaded from the National Center of Biotechnology Information (NCBI) Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/ geo/) which was based on GPL96 platform of (HG-U133A) Affymetrix Human Genome U133A Array. In this study, gene microarray data of 5 conventional OS samples (including 2 females and 3 males, the age ranging from 7 to 74 years old, the grade from 2 to 3) with 2 replicates and 4 OS pulmonary metastasis samples (including 3 females and 1 male, the age ranging from 21 to 45 years old, the grade from 1 to 3) in duplicate were obtained.…”

Section: Methodsmentioning

confidence: 99%

“…Therefore, more researchers made use of bioinformatics methods to analyze the information of GSE14359 offered by Guenther et al [15] who analyzed the expression of EphA2 in OS and the activation of the mitogenic signaling pathway. A previous study has demonstrated that some pathways play important roles in the progression of OS such as phosphatidylinositol 3-kinase (PI3K)/AKT pathway, antigen processing and presentation, focal adhesion and adherens junction [16].…”

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confidence: 99%

Identification of biomarkers for metastatic osteosarcoma based on DNA microarray data

Wang¹

2015

neo

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Osteosarcoma (OS) is a malignant bone tumor very often with pulmonary metastasis and is the main cause of OS mortality. The objective of this study was to screen for possible biomarkers of metastatic OS to explore the mechanisms of pulmonary metastasis of OS through network construction. GSE14359 was downloaded from the Gene Expression Omnibus database, which included 5 samples from conventional OS group with 2 replicates and 4 samples from OS pulmonary metastasis group in duplicate. Differentially expressed genes (DEGs) between two groups were identified by limma packages in R and classical t-test with the threshold of the false discovery rate (FDR) <0.05. The Database for Annotation, Visualization and Integrated Discovery (DAVID) were then used to perform functional annotation (FDR < 0.01). Differential coexpression network was constructed with subspace differential coexpression analysis (SDC), and genes with high degrees in the differential coexpression network were identified.A total of 1344 genes were screened as DEGs, including 677 up-and 667 down-regulated DEGs in the pulmonary metastasis of OS. Thirty-one significantly enriched functions were obtained, such as blood vessel morphogenesis, defense response, cell death and so on. DEGs with high degrees (brain-specific angiogenesis inhibitor 2 (BAI2), formin-like 1 (FMNL1), dualspecificity phosphatase 7 (DUSP7), transient receptor potential melastatin 2 (TRPM2), CBP80/20-dependent translation initiation factor (KIAA0427) and C120rf35) in the differential coexpression network were found. BAI2, FMNL1, DUSP7 and TRPM2 may be useful markers for predicting tumor metastasis and therapeutic targets for the treatment of OS patients with metastasis. Key words: osteosarcoma, differentially expressed genes, differential coexpression network, gene ontologyOsteosarcoma (OS) is the most common primary malignant cancer of the bone in both children and young adults [1]. Moreover, approximately 15-20% of patients present with discernable metastasis [2], frequently for lung [3]. Though the overall recurrent-free survival rate over 5 years remains approximately 65% with neoadjuvant chemotherapy combined with surgery, while when pulmonary metastasis, less than 30% [4]. In addition, neoadjuvant chemotherapy remains controversial in the world [5]. The treatment for OS is very challenging. Hence, it is important to identify molecular targets to prevent pulmonary metastases during the early stage, and further to improve the prognosis of OS patients.The underlying pathogenesis has been difficult to establish because of its heterogeneous histology and complex etiology. Extensive efforts have been made to explore the potential etiology and molecular mechanisms. Reversion-inducing cysteine rich protein with Kazal motifs (RECK), a member of antiangiogenic factors, is down-regulated in OS [6]. The expression level of TGF-β1 is significantly higher in high-grade OS than low-grade OS [7]. Densmore et al. have shown that p53 can effectively reduce the number and the size of lung metastases ...

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De novo expression of EphA2 in osteosarcoma modulates activation of the mitogenic signalling pathway

Abstract: Upregulation and de novo expression of ephrins in osteosarcomas are involved in oncogenic signalling and thus might stimulate osteosarcoma metastasis.

Cited by 61 publications

References 33 publications

Structural and Functional Characterization of Monomeric EphrinA1 Binding Site to EphA2 Receptor

Structural and Functional Characterization of Monomeric EphrinA1 Binding Site to EphA2 Receptor

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

Identification of biomarkers for metastatic osteosarcoma based on DNA microarray data

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