更新于：2024-05-01
EphB4
B型肝配蛋白受体-4
更新于：2024-05-01
基本信息
别名 EphB4受体、EPH receptor B4、EPHB4 + [6] |
简介 Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Together with its cognate ligand/functional ligand EFNB2 it is involved in the regulation of cell adhesion and migration, and plays a central role in heart morphogenesis, angiogenesis and blood vessel remodeling and permeability. EPHB4-mediated forward signaling controls cellular repulsion and segregation from EFNB2-expressing cells. |
关联
靶点 |
作用机制 |
在研机构 |
原研机构 |
在研适应症 |
非在研适应症 |
最高研发阶段 |
首次获批国家/地区 |
首次获批日期 |
靶点 |
作用机制 |
在研机构 |
原研机构 |
在研适应症 |
非在研适应症 |
最高研发阶段 |
首次获批国家/地区 |
首次获批日期 |
靶点 |
作用机制 |
在研机构 |
原研机构 |
在研适应症 |
非在研适应症 |
最高研发阶段 |
首次获批国家/地区 |
首次获批日期 |
A First-in-Human Phase I Study of Intravesical sEphB4-HSA in Patients With "BCG-Unresponsive" Bladder Carcinoma In Situ (CIS), Completely Resected High Grade Ta/T1, to Establish the Maximum Tolerated Dose (MTD) or Recommended Phase II Dose (RP2D)
A Phase II Study of sEphB4-HSA in Kaposi Sarcoma
A Phase II Trial of Pembrolizumab as Standard of Care + sEphB4-HSA in Chemotherapy Ineligible or Chemotherapy Refusing Patients With Metastatic Urothelial Carcinoma
100 项与 EphB4 相关的临床结果
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100 项与 EphB4 相关的转化医学
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2024-01-17Cancer research
Inhibition of Ephrin B2 Reverse Signaling Suppresses Multiple Myeloma Pathogenesis.
Article
作者: Joshua P Sasine ; Natalia Y Kozlova ; Lisa Valicente ; Jennifer Dukov ; Dana H Tran ; Heather A Himburg ; Sanjeev Kumar ; Sarah Khorsandi ; Aldi Chan ; Samantha Grohe ; Michelle Li ; Jenny Kan ; Mary E Sehl ; Gary J Schiller ; Bryanna Reinhardt ; Brijesh Kumar Singh ; Ritchie Ho ; Peibin Yue ; Elena B Pasquale ; John P Chute
Bone marrow vascular endothelial cells (BM ECs) regulate multiple myeloma (MM) pathogenesis. Identification of the mechanisms underlying this interaction could lead to the development of improved strategies for treating MM. Here, we performed a transcriptomic analysis of human ECs with high capacity to promote MM growth, revealing overexpression of the receptor tyrosine kinases, EPHB1 and EPHB4, in MM - supportive ECs. Expression of ephrin B2 (EFNB2), the binding partner for EPHB1 and EPHB4, was significantly increased in MM cells. Silencing EPHB1 or EPHB4 in ECs suppressed MM growth in co-culture. Similarly, loss of EFNB2 in MM cells blocked MM proliferation and survival in vitro, abrogated MM engraftment in immune-deficient mice, and increased MM sensitivity to chemotherapy. Administration of an EFNB2-targeted single chain variable fragment also suppressed MM growth in vivo. In contrast, overexpression of EFNB2 in MM cells increased STAT5 activation, increased MM cell survival and proliferation, and decreased MM sensitivity to chemotherapy. Conversely, expression of mutant EFNB2 lacking reverse signaling capacity in MM cells increased MM cell death and sensitivity to chemotherapy and abolished MM growth in vivo. Complementary analysis of MM patient data revealed that increased EFNB2 expression is associated with adverse-risk disease and decreased survival. This study suggests that EFNB2 reverse signaling controls MM pathogenesis and can be therapeutically targeted to improve MM outcomes.
2024-01-04Scientific reports
ADAMTS13 regulates angiogenic markers via Ephrin/Eph signaling in human mesenchymal stem cells under serum-deprivation stress.
Article
作者: Srishti Dutta Gupta ; Malancha Ta
Mesenchymal stem cells (MSCs) are known to facilitate angiogenesis and promote neo-vascularization via secretion of trophic factors. Here, we explored the molecular mechanism adopted by ADAMTS13 in modulating the expression of some key angiogenic markers in human umbilical cord-derived MSCs under serum-deprivation stress. Wharton's jelly MSCs (WJ-MSCs) were isolated from the perivascular region of human umbilical cords by explant culture. ADAMTS13 was upregulated at both mRNA and protein levels in WJ-MSCs under serum-deprivation stress. Correspondingly, some key angiogenic markers were also seen to be upregulated. By screening signaling pathways, p38 and JNK pathways were identified as negative and positive regulators for expression of ADAMTS13, and the angiogenic markers, respectively. Our results also indicated the Notch pathway and p53 as other probable partners modulating the expression of ADAMTS13 and the angiogenic markers. Knockdown of ADAMTS13 using siRNA led to reversal in the expression of these angiogenic markers. Further, ADAMTS13 was shown to act via the EphrinB2/EphB4 axis followed by ERK signaling to control expression of the angiogenic markers. Interestingly, stronger expression levels were noted for ADAMTS13, VEGF and PDGF under a more stringent nutrient stress condition. Thus, we highlight a novel role of ADAMTS13 in WJ-MSCs under nutrient stress condition.
2023-12-27Cellular and molecular neurobiology
Discovery and Characterization of Ephrin B2 and EphB4 Dysregulation and Novel Mutations in Cerebral Cavernous Malformations: In Vitro and Patient-Derived Evidence of Ephrin-Mediated Endothelial Cell Pathophysiology.
Article
作者: Julie Sesen ; Aram Ghalali ; Jessica Driscoll ; Tyra Martinez ; Adrien Lupieri ; David Zurakowski ; Sanda Alexandrescu ; Edward R Smith ; Katie P Fehnel
Intracranial vascular malformations manifest on a continuum ranging from predominantly arterial to predominantly venous in pathology. Cerebral cavernous malformations (CCMs) are capillary malformations that exist at the midpoint of this continuum. The axon guidance factor Ephrin B2 and its receptor EphB4 are critical regulators of vasculogenesis in the developing central nervous system. Ephrin B2/EphB4 dysregulation has been implicated in the pathogenesis of arterial-derived arteriovenous malformations and vein-based vein of Galen malformations. Increasing evidence supports the hypothesis that aberrant Ephrin B2/EphB4 signaling may contribute to developing vascular malformations, but their role in CCMs remains largely uncharacterized. Evidence of Ephrin dysregulation in CCMs would be important to establish a common link in the pathogenic spectrum of EphrinB2/Ephb4 dysregulation. By studying patient-derived primary CCM endothelial cells (CCMECs), we established that CCMECs are functionally distinct from healthy endothelial cell controls; CCMECs demonstrated altered patterns of migration, motility, and impaired tube formation. In addition to the altered phenotype, the CCMECs also displayed an increased ratio of EphrinB2/EphB4 compared to the healthy endothelial control cells. Furthermore, whole exome sequencing identified mutations in both EphrinB2 and EphB4 in the CCMECs. These findings identify functional alterations in the EphrinB2/EphB4 ratio as a feature linking pathophysiology across the spectrum of arterial, capillary, and venous structural malformations in the central nervous system while revealing a putative therapeutic target.
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