scholarly journals Eph receptors inactivate R-Ras through different mechanisms to achieve cell repulsion

2006 ◽  
Vol 119 (7) ◽  
pp. 1244-1254 ◽  
Author(s):  
M. Dail
Keyword(s):  
Eph Receptors ◽  
Cell Repulsion

scholarly journals Myosin 1b functions as an effector of EphB signaling to control cell repulsion

2015 ◽  
Vol 210 (2) ◽  
pp. 347-361 ◽  
Author(s):  
Marie-Thérèse Prospéri ◽  
Priscilla Lépine ◽  
Florent Dingli ◽  
Perrine Paul-Gilloteaux ◽  
René Martin ◽  
...  
Keyword(s):  
Cell Morphology ◽  
Morphological Changes ◽  
Control Cell ◽  
Dependent Manner ◽  
Eph Receptors ◽  
Actin Remodeling ◽  
Actin Cortex ◽  
Cell Segregation ◽  
Tethered Ligands ◽  
Cell Repulsion

Eph receptors and their membrane-tethered ligands, the ephrins, have important functions in embryo morphogenesis and in adult tissue homeostasis. Eph/ephrin signaling is essential for cell segregation and cell repulsion. This process is accompanied by morphological changes and actin remodeling that drives cell segregation and tissue patterning. The actin cortex must be mechanically coupled to the plasma membrane to orchestrate the cell morphology changes. Here, we demonstrate that myosin 1b that can mechanically link the membrane to the actin cytoskeleton interacts with EphB2 receptors via its tail and is tyrosine phosphorylated on its tail in an EphB2-dependent manner. Myosin 1b regulates the redistribution of myosin II in actomyosin fibers and the formation of filopodia at the interface of ephrinB1 and EphB2 cells, which are two processes mediated by EphB2 signaling that contribute to cell repulsion. Together, our results provide the first evidence that a myosin 1 functions as an effector of EphB2/ephrinB signaling, controls cell morphology, and thereby cell repulsion.

scholarly journals Tiam–Rac signaling mediates trans-endocytosis of ephrin receptor EphB2 and is important for cell repulsion

2016 ◽  
Vol 214 (6) ◽  
pp. 735-752 ◽  
Author(s):  
Thomas N. Gaitanos ◽  
Jorg Koerner ◽  
Ruediger Klein
Keyword(s):  
Eph Receptors ◽  
Nucleotide Exchange ◽  
Guanine Nucleotide Exchange ◽  
Nucleotide Exchange Factor ◽  
Ephb Receptors ◽  
Rho Family Gtpases ◽  
Ephrin Ligands ◽  
Membrane Bound ◽  
In Trans ◽  
Cell Repulsion

Ephrin receptors interact with membrane-bound ephrin ligands to regulate contact-mediated attraction or repulsion between opposing cells, thereby influencing tissue morphogenesis. Cell repulsion requires bidirectional trans-endocytosis of clustered Eph–ephrin complexes at cell interfaces, but the mechanisms underlying this process are poorly understood. Here, we identified an actin-regulating pathway allowing ephrinB+ cells to trans-endocytose EphB receptors from opposing cells. Live imaging revealed Rac-dependent F-actin enrichment at sites of EphB2 internalization, but not during vesicle trafficking. Systematic depletion of Rho family GTPases and their regulatory proteins identified the Rac subfamily and the Rac-specific guanine nucleotide exchange factor Tiam2 as key components of EphB2 trans-endocytosis, a pathway previously implicated in Eph forward signaling, in which ephrins act as in trans ligands of Eph receptors. However, unlike in Eph signaling, this pathway is not required for uptake of soluble ligands in ephrinB+ cells. We also show that this pathway is required for EphB2-stimulated contact repulsion. These results support the existence of a conserved pathway for EphB trans-endocytosis that removes the physical tether between cells, thereby enabling cell repulsion.

The role of ephrins and Eph receptors in cancer

2004 ◽  
Vol 15 (6) ◽  
pp. 419-433 ◽  
Author(s):  
Hanna Surawska ◽  
Patrick C. Ma ◽  
Ravi Salgia
Keyword(s):  
Eph Receptors

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.

scholarly journals EphA2 and EGFR: Friends in Life, Partners in Crime. Can EphA2 Be a Predictive Biomarker of Response to Anti-EGFR Agents?

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 700
Author(s):  
Mario Cioce ◽  
Vito Michele Fazio
Keyword(s):  
Colorectal Cancer ◽  
Solid Tumors ◽  
Receptor Tyrosine Kinase ◽  
Predictive Biomarker ◽  
Eph Receptors ◽  
Oncogenic Signaling ◽  
Induced Stress ◽  
Molecular Determinants ◽  
Signaling Axis ◽  
Context Specific

The Eph receptors represent the largest group among Receptor Tyrosine kinase (RTK) families. The Eph/ephrin signaling axis plays center stage during development, and the deep perturbation of signaling consequent to its dysregulation in cancer reveals the multiplicity and complexity underlying its function. In the last decades, they have emerged as key players in solid tumors, including colorectal cancer (CRC); however, what causes EphA2 to switch between tumor-suppressive and tumor-promoting function is still an active theater of investigation. This review summarizes the recent advances in understanding EphA2 function in cancer, with detail on the molecular determinants of the oncogene-tumor suppressor switch function of EphA2. We describe tumor context-specific examples of EphA2 signaling and the emerging role EphA2 plays in supporting cancer—stem—cell-like populations and overcoming therapy-induced stress. In such a frame, we detail the interaction of the EphA2 and EGFR pathway in solid tumors, including colorectal cancer. We discuss the contribution of the EphA2 oncogenic signaling to the resistance to EGFR blocking agents, including cetuximab and TKIs.

Eph receptors and ephrins in neural development

1999 ◽  
Vol 9 (1) ◽  
pp. 65-73 ◽  
Author(s):  
Dennis DM O'Leary ◽  
David G Wilkinson
Keyword(s):  
Neural Development ◽  
Eph Receptors

Tyrosine Phosphorylation of Transmembrane Ligands for Eph Receptors

Science ◽  
1997 ◽  
Vol 275 (5306) ◽  
pp. 1640-1643 ◽  
Author(s):  
K. Bruckner ◽  
E. B. Pasquale ◽  
R. Klein
Keyword(s):  
Tyrosine Phosphorylation ◽  
Eph Receptors

Expression of Eph Receptors and their Ligands in Palate

2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
Maria J Serrano ◽  
Symone San Miguel ◽  
Ashneet Sachar ◽  
Kathy Svoboda ◽  
M Douglas Benson
Keyword(s):  
Eph Receptors
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