scholarly journals Differential Expression Patterns of Eph Receptors and Ephrin Ligands in Human Cancers

2018 ◽  
Vol 2018 ◽  
pp. 1-23 ◽  
Author(s):  
Chung-Ting Jimmy Kou ◽  
Raj P. Kandpal
Keyword(s):  
Differential Expression ◽  
Tyrosine Kinases ◽  
Neuronal Development ◽  
Transmembrane Domain ◽  
Tissue Injury ◽  
Expression Patterns ◽  
Cancer Therapeutics ◽  
Eph Receptors ◽  
Human Cancers ◽  
Ephrin Ligands

Eph receptors constitute the largest family of receptor tyrosine kinases, which are activated by ephrin ligands that either are anchored to the membrane or contain a transmembrane domain. These molecules play important roles in the development of multicellular organisms, and the physiological functions of these receptor-ligand pairs have been extensively documented in axon guidance, neuronal development, vascular patterning, and inflammation during tissue injury. The recognition that aberrant regulation and expression of these molecules lead to alterations in proliferative, migratory, and invasive potential of a variety of human cancers has made them potential targets for cancer therapeutics. We present here the involvement of Eph receptors and ephrin ligands in lung carcinoma, breast carcinoma, prostate carcinoma, colorectal carcinoma, glioblastoma, and medulloblastoma. The aberrations in their abundances are described in the context of multiple signaling pathways, and differential expression is suggested as the mechanism underlying tumorigenesis.

scholarly journals Structural and Functional Insights into the Transmembrane Domain Association of Eph Receptors

2021 ◽  
Vol 22 (16) ◽  
pp. 8593
Author(s):  
Amita R. Sahoo ◽  
Matthias Buck
Keyword(s):  
Tyrosine Kinases ◽  
Transmembrane Domain ◽  
Eph Receptors ◽  
Adult Tissue ◽  
Eph Receptor ◽  
Transmembrane Peptides ◽  
Future Studies ◽  
Functional Aspects ◽  
Ephrin Ligands ◽  
Dynamics Simulations

Eph receptors are the largest family of receptor tyrosine kinases and by interactions with ephrin ligands mediate a myriad of processes from embryonic development to adult tissue homeostasis. The interaction of Eph receptors, especially at their transmembrane (TM) domains is key to understanding their mechanism of signal transduction across cellular membranes. We review the structural and functional aspects of EphA1/A2 association and the techniques used to investigate their TM domains: NMR, molecular modelling/dynamics simulations and fluorescence. We also introduce transmembrane peptides, which can be used to alter Eph receptor signaling and we provide a perspective for future studies.

A role for the EphA family in the topographic targeting of vomeronasal axons

Development ◽  
2001 ◽  
Vol 128 (6) ◽  
pp. 895-906
Author(s):  
B. Knoll ◽  
K. Zarbalis ◽  
W. Wurst ◽  
U. Drescher
Keyword(s):  
Tyrosine Kinases ◽  
Expression Patterns ◽  
Eph Receptors ◽  
Accessory Olfactory Bulb ◽  
In Vivo Experiments ◽  
Receptor Concentration ◽  
High Ligand

We have investigated the role of the Eph family of receptor tyrosine kinases and their ligands in the establishment of the vomeronasal projection in the mouse. Our data show intriguing differential expression patterns of ephrin-A5 on vomeronasal axons and of EphA6 in the accessory olfactory bulb (AOB), such that axons with high ligand concentration project onto regions of the AOB with high receptor concentration and vice versa. These data suggest a mechanism for development of this projection that is the opposite of the repellent interaction between Eph receptors and ligands observed in other systems. In support of this idea, when given the choice of whether to grow on lanes containing EphA-F(c)/laminin or F(c)/laminin protein (in the stripe assay), vomeronasal axons prefer to grow on EphA-F(c)/laminin. Analysis of ephrin-A5 mutant mice revealed a disturbance of the topographic targeting of vomeronasal axons to the AOB. In summary, these data, which are derived from in vitro and in vivo experiments, indicate an important role of the EphA family in setting up the vomeronasal projection.

scholarly journals ELF-2, a new member of the Eph ligand family, is segmentally expressed in mouse embryos in the region of the hindbrain and newly forming somites.

1995 ◽  
Vol 15 (9) ◽  
pp. 4921-4929 ◽  
Author(s):  
A D Bergemann ◽  
H J Cheng ◽  
R Brambilla ◽  
R Klein ◽  
J G Flanagan
Keyword(s):  
Tyrosine Kinases ◽  
Dissociation Constants ◽  
Expression Patterns ◽  
Mouse Embryos ◽  
Eph Receptors ◽  
Vertebrate Development ◽  
Orphan Receptors ◽  
Free System ◽  
A Cell

The Eph receptors are the largest known family of receptor tyrosine kinases and are notable for distinctive expression patterns in the nervous system and in early vertebrate development. However, all were identified as orphan receptors, and only recently have there been descriptions of a corresponding family of ligands. We describe here a new member of the Eph ligand family, designated ELF-2 (Eph ligand family 2). The cDNA sequence for mouse ELF-2 indicates that it is a transmembrane ligand. It shows closest homology to the other known transmembrane ligand in the family, ELK-L/LERK-2/Cek5-L, with 57% identity in the extracellular domain. There is also striking homology in the cytoplasmic domain, including complete identity of the last 33 amino acids, suggesting intracellular interactions. On cell surfaces, and in a cell-free system, ELF-2 binds to three closely related Eph family receptors, Elk, Cek10 (apparent ortholog of Sek-4 and HEK2), and Cek5 (apparent ortholog of Nuk/Sek-3), all with dissociation constants of approximately 1 nM. In situ hybridization of mouse embryos shows ELF-2 RNA expression in a segmental pattern in the hindbrain region and the segmenting mesoderm. Comparable patterns have been described for Eph family receptors, including Sek-4 and Nuk/Sek-3, suggesting roles for ELF-2 in patterning these regions of the embryo.

Differential expression of a transcription regulatory factor, the LIM domain only 4 protein Lmo4, in muscle sensory neurons

Development ◽  
2002 ◽  
Vol 129 (21) ◽  
pp. 4879-4889
Author(s):  
Hsiao-Huei Chen ◽  
Joseph W. Yip ◽  
Alexandre F. R. Stewart ◽  
Eric Frank
Keyword(s):  
Differential Expression ◽  
Sensory Neurons ◽  
Molecular Mechanisms ◽  
Neuronal Development ◽  
Expression Patterns ◽  
Cdna Libraries ◽  
Homeodomain Protein ◽  
Lim Domain ◽  
Homeodomain Proteins ◽  
Lim Homeodomain

In the stretch-reflex system, proprioceptive sensory neurons make selective synaptic connections with different subsets of motoneurons, according to the peripheral muscles they supply. To examine the molecular mechanisms that may influence the selection of these synaptic targets, we constructed single-cell cDNA libraries from sensory neurons that innervate antagonist muscles. Differential screening of these libraries identified a transcription regulatory co-factor of the LIM homeodomain proteins, the LIM domain only 4 protein Lmo4, expressed in most adductor but few sartorius sensory neurons. Differential patterns of Lmo4 expression were also seen in sensory neurons supplying three other muscles. A subset of motoneurons also expresses Lmo4 but the pattern of expression is not specific for motor pools. Differential expression of Lmo4 occurs early, as neurons develop their characteristic LIM homeodomain protein expression patterns. Moreover, ablation of limb buds does not block Lmo4 expression, suggesting that an intrinsic program controls the early differential expression of Lmo4. LIM homeodomain proteins are known to regulate several aspects of sensory and motor neuronal development. Our results suggest that Lmo4 may participate in this differentiation by regulating the transcriptional activity of LIM homeodomain proteins.

scholarly journals Evaluation of the Anti-Tumor Activity of Small Molecules Targeting Eph/Ephrins in APC min/J Mice

2020 ◽  
Vol 13 (4) ◽  
pp. 69
Author(s):  
Miriam Corrado ◽  
Carmine Giorgio ◽  
Elisabetta Barocelli ◽  
Giuseppe Vittucci Marzetti ◽  
Anna Maria Cantoni ◽  
...  
Keyword(s):  
Small Molecules ◽  
Tyrosine Kinases ◽  
Tumor Development ◽  
Eph Receptors ◽  
Pharmacological Approach ◽  
Ephrin Ligands ◽  
Prevent Tumor Growth ◽  
First Time ◽  
Anti Tumor Activity

The Eph receptors are the largest receptors tyrosine kinases (RTKs) family in humans and together with ephrin ligands constitute a complex cellular communication system often dysregulated in many tumors. The role of the Eph-ephrin system in colorectal cancer (CRC) has been investigated and different expression of Eph receptors have been associated with tumor development and progression. In light of this evidence, we investigated if a pharmacological approach aimed at inhibiting Eph/ephrin interaction through small molecules could prevent tumor growth in APC min/J mice. The 8-week treatment with the Eph-ephrin antagonist UniPR129 significantly reduced the number of adenomas in the ileum and decreased the diameter of adenomas in the same region. Overall our data suggested as UniPR129 could be able to slow down the tumor development in APC min/J mice. These results further confirm literature data about Eph kinases as a new valuable target in the intestinal cancer and for the first time showed the feasibility of the Eph-ephrin inhibition as a useful pharmacological approach against the intestinal tumorigenesis. In conclusion this work paves the way for further studies with Eph-ephrin inhibitors in order to confirm the Eph antagonism as innovative pharmacological approach with preventive benefit in the intestinal tumor development.

Complex expression patterns of Eph receptor tyrosine kinases and their ephrin ligands in colorectal carcinogenesis

2012 ◽  
Vol 48 (5) ◽  
pp. 753-762 ◽  
Author(s):  
Nirmitha I. Herath ◽  
Mark D. Spanevello ◽  
James D. Doecke ◽  
Fiona M. Smith ◽  
Celio Pouponnot ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Expression Patterns ◽  
Colorectal Carcinogenesis ◽  
Eph Receptor ◽  
Ephrin Ligands ◽  
Complex Expression

scholarly journals Exosomes mediate cell contact–independent ephrin-Eph signaling during axon guidance

2016 ◽  
Vol 214 (1) ◽  
pp. 35-44 ◽  
Author(s):  
Jingyi Gong ◽  
Roman Körner ◽  
Louise Gaitanos ◽  
Rüdiger Klein
Keyword(s):  
Neural Development ◽  
Tyrosine Kinases ◽  
Neuronal Development ◽  
Cell Types ◽  
Cell Contact ◽  
Eph Receptor ◽  
Endosomal Sorting ◽  
Ephrin Ligands ◽  
Direct Cell ◽  
Mediate Cell

The cellular release of membranous vesicles known as extracellular vesicles (EVs) or exosomes represents a novel mode of intercellular communication. Eph receptor tyrosine kinases and their membrane-tethered ephrin ligands have very important roles in such biologically diverse processes as neuronal development, plasticity, and pathological diseases. Until now, it was thought that ephrin-Eph signaling requires direct cell contact. Although the biological functions of ephrin-Eph signaling are well understood, our mechanistic understanding remains modest. Here we report the release of EVs containing Ephs and ephrins by different cell types, a process requiring endosomal sorting complex required for transport (ESCRT) activity and regulated by neuronal activity. Treatment of cells with purified EphB2+ EVs induces ephrinB1 reverse signaling and causes neuronal axon repulsion. These results indicate a novel mechanism of ephrin-Eph signaling independent of direct cell contact and proteolytic cleavage and suggest the participation of EphB2+ EVs in neural development and synapse physiology.

Analysis of the Differential Expression Patterns of Sumoylation Enzymes E1, E2 and E3 in Ocular Cell Lines

2019 ◽  
Vol 18 (8) ◽  
pp. 509-515 ◽  
Author(s):  
Qian Nie ◽  
Jie Xie ◽  
Xiaodong Gong ◽  
Zhongwen Luo ◽  
Ling Wang ◽  
...  
Keyword(s):  
Differential Expression ◽  
Cell Lines ◽  
Expression Patterns

scholarly journals Differential expression and correlation analysis of miRNA–mRNA profiles in swine testicular cells infected with porcine epidemic diarrhea virus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiaoqian Zhang ◽  
Chang Li ◽  
Bingzhou Zhang ◽  
Zhonghua Li ◽  
Wei Zeng ◽  
...  
Keyword(s):  
Differential Expression ◽  
Porcine Epidemic Diarrhea Virus ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Bacterial Invasion ◽  
Sequencing Data ◽  
Diarrhea Virus ◽  
Comparison Groups ◽  
Porcine Epidemic Diarrhea

AbstractThe variant virulent porcine epidemic diarrhea virus (PEDV) strain (YN15) can cause severe porcine epidemic diarrhea (PED); however, the attenuated vaccine-like PEDV strain (YN144) can induce immunity in piglets. To investigate the differences in pathogenesis and epigenetic mechanisms between the two strains, differential expression and correlation analyses of the microRNA (miRNA) and mRNA in swine testicular (ST) cells infected with YN15, YN144, and mock were performed on three comparison groups (YN15 vs Control, YN144 vs Control, and YN15 vs YN144). The mRNA and miRNA expression profiles were obtained using next-generation sequencing (NGS), and the differentially expressed (DE) (p-value < 0.05) mRNA and miRNA were obtained using DESeq R package. mRNAs targeted by DE miRNAs were predicted using the miRanda algortithm. 8039, 8631 and 3310 DE mRNAs, and 36, 36, and 22 DE miRNAs were identified in the three comparison groups, respectively. 14,140, 15,367 and 3771 DE miRNA–mRNA (targeted by DE miRNAs) interaction pairs with negatively correlated expression patterns were identified, and interaction networks were constructed using Cytoscape. Six DE miRNAs and six DE mRNAs were randomly selected to verify the sequencing data by real-time relative quantitative reverse transcription polymerase chain reaction (qRT-PCR). Based on bioinformatics analysis, we discovered the differences were mostly involved in host immune responses and viral pathogenicity, including NF-κB signaling pathway and bacterial invasion of epithelial cells, etc. This is the first comprehensive comparison of DE miRNA–mRNA pairs in YN15 and YN144 infection in vitro, which could provide novel strategies for the prevention and control of PED.

scholarly journals The Value of EphB2 Receptor and Cognate Ephrin Ligands in Prognostic and Predictive Assessments of Human Breast Cancer

2021 ◽  
Vol 22 (15) ◽  
pp. 8098
Author(s):  
Abdul Shukkur Ebrahim ◽  
Zeyad Hailat ◽  
Sudeshna Bandyopadhyay ◽  
Daniel Neill ◽  
Mustapha Kandouz
Keyword(s):  
Breast Cancer ◽  
Distant Metastasis ◽  
Predictive Value ◽  
Intracellular Signaling ◽  
Ductal Carcinoma ◽  
Cancer Development ◽  
Eph Receptors ◽  
Free Survival ◽  
Expression Levels ◽  
Ephrin Ligands

Cell–cell communication proteins Eph and ephrin constitute the largest family of receptor tyrosine kinases (RTKs). They are distinguished by the fact that both receptors and ligands are membrane-bound, and both can drive intracellular signaling in their respective cells. Ever since these RTKs have been found to be involved in cancer development, strategies to target them therapeutically have been actively pursued. However, before this goal can be rationally achieved, the contributions of either Eph receptors or their ephrin ligands to cancer development and progression should be scrutinized in depth. To assess the clinical pertinence of this concern, we performed a systematic review and meta-analysis of the prognostic/predictive value of EphB2 and its multiple cognate ephrin ligands in breast cancer. We found that EphB2 has prognostic value, as indicated by the association of higher EphB2 expression levels with lower distant metastasis-free survival (DMFS), and the association of lower EphB2 expression levels with poorer relapse-free survival (RFS). We also found that higher EphB2 expression could be a prognostic factor for distant metastasis, specifically in the luminal subtypes of breast cancer. EFNB2 showed a marked correlation between higher expression levels and shorter DMFS. EFNA5 or EFNB1 overexpression is correlated with longer RFS. Increased EFNB1 expression is correlated with longer OS in lymph node (LN)-negative patients and the luminal B subtype. Higher levels of EFNB2 or EFNA5 are significantly correlated with shorter RFS, regardless of LN status. However, while this correlation with shorter RFS is true for EFNB2 in all subtypes except basal, it is also true for EFNA5 in all subtypes except HER2+. The analysis also points to possible predictive value for EphB2. In systemically treated patients who have undergone either endocrine therapy or chemotherapy, we found that higher expression of EphB2 is correlated with better rates of RFS. Bearing in mind the limitations inherent to any mRNA-based profiling method, we complemented our analysis with an immunohistochemical assessment of expression levels of both the EphB2 receptor and cognate ephrin ligands. We found that the latter are significantly more expressed in cancers than in normal tissues, and even more so in invasive and metastatic samples than in ductal carcinoma in situ (DCIS). Finally, in an in vitro cellular model of breast cancer progression, based on H-Ras-transformation of the MCF10A benign mammary cell line, we observed dramatic increases in the mRNA expression of EphB2 receptor and EFNB1 and EFNB2 ligands in transformed and invasive cells in comparison with their benign counterparts. Taken together, these data show the clinical validity of a model whereby EphB2, along with its cognate ephrin ligands, have dual anti- and pro-tumor progression effects. In so doing, they reinforce the necessity of further biological investigations into Ephs and ephrins, prior to using them in targeted therapies.

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