Dysregulated erythropoietin-producing hepatocellular receptor A2 (EphA2) is involved in tubal pregnancy via regulating cell adhesion of the Fallopian tube epithelial cells

Jiang, Huan; Yang, Xiuyan; Zhu, Weijie

doi:10.1186/s12958-018-0403-5

Cited by 3 publications

(1 citation statement)

References 34 publications

(41 reference statements)

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“…53 Further studies revealed that EphA2 was widely expressed in human Fallopian tube epithelium in a temporospatialindependent manner, and the inactivated EphA2 could enhance the tubal stickiness in women with tubal pregnancy. 54 FAK is activated by β1 integrin via its autophosphorylation (Pho-FAK). Both integrin and FAK signaling are suggested to play important roles in uterine implantation because they facilitate cell adhesion.…”

Section: The Adhesion Stage Of Tubal Implantationmentioning

confidence: 99%

Interaction networks between the Fallopian tubes and the embryo in human tubal pregnancy: Current knowledge and perspectives

Jiang

Jian-xiong

2021

J of Obstet and Gynaecol

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Aim: More than 90% of ectopic pregnancies occur in the Fallopian tubes. As the pathogenesis of tubal pregnancy remains largely unclear, the development of strategies to prevent and treat tubal pregnancy still represents a major clinical challenge. This review thoroughly summarizes the current data, aiming to determine the genes and signaling pathways that are involved in the pathophysiology of human tubal pregnancy. Methods: An electronic search from databases of PubMed, Google Scholar, and Chinese databases was carried out using key words pertaining to the pathogenesis of tubal pregnancy from the perspectives of both the Fallopian tubes and the embryo. A review of the literatures including review articles, experimental, and observational studies and case reports published between 1999 and 2021 was conducted. Results: Tubal pregnancy results from the interaction networks between the Fallopian tube and the embryo rather than from simple tubal abnormality. Furthermore, the embryo-maternal communication is supposed to start from the preimplantation period to the implantation period. Conclusion: A greater understanding of the interaction networks between the Fallopian tubes and the embryo is of great significance for the prevention and medical treatment of tubal pregnancy.

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Section: The Adhesion Stage Of Tubal Implantationmentioning

confidence: 99%

Interaction networks between the Fallopian tubes and the embryo in human tubal pregnancy: Current knowledge and perspectives

Jiang

Jian-xiong

2021

J of Obstet and Gynaecol

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Identification of potent pan-ephrin receptor kinase inhibitors using DNA-encoded chemistry technology

Madasu,

Liao,

Parks

et al. 2024

Proc. Natl. Acad. Sci. U.S.A.

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EPH receptors (EPHs), the largest family of tyrosine kinases, phosphorylate downstream substrates upon binding of ephrin cell surface–associated ligands. In a large cohort of endometriotic lesions from individuals with endometriosis, we found that EPHA2 and EPHA4 expressions are increased in endometriotic lesions relative to normal eutopic endometrium. Because signaling through EPHs is associated with increased cell migration and invasion, we hypothesized that chemical inhibition of EPHA2/4 could have therapeutic value. We screened DNA-encoded chemical libraries (DECL) to rapidly identify EPHA2/4 kinase inhibitors. Hit compound, CDD-2693, exhibited picomolar/nanomolar kinase activity against EPHA2 (K i : 4.0 nM) and EPHA4 (K i : 0.81 nM). Kinome profiling revealed that CDD-2693 bound to most EPH family and SRC family kinases. Using NanoBRET target engagement assays, CDD-2693 had nanomolar activity versus EPHA2 (IC 50 : 461 nM) and EPHA4 (IC 50 : 40 nM) but was a micromolar inhibitor of SRC, YES, and FGR. Chemical optimization produced CDD-3167, having picomolar biochemical activity toward EPHA2 (K i : 0.13 nM) and EPHA4 (K i : 0.38 nM) with excellent cell-based potency EPHA2 (IC 50 : 8.0 nM) and EPHA4 (IC 50 : 2.3 nM). Moreover, CDD-3167 maintained superior off-target cellular selectivity. In 12Z endometriotic epithelial cells, CDD-2693 and CDD-3167 significantly decreased EFNA5 (ligand) induced phosphorylation of EPHA2/4, decreased 12Z cell viability, and decreased IL-1β-mediated expression of prostaglandin synthase 2 ( PTGS2 ). CDD-2693 and CDD-3167 decreased expansion of primary endometrial epithelial organoids from patients with endometriosis and decreased Ewing’s sarcoma viability. Thus, using DECL, we identified potent pan-EPH inhibitors that show specificity and activity in cellular models of endometriosis and cancer.

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Ephrin and Eph receptor signaling in female reproductive physiology and pathology†

Adu‐Gyamfi

Czika

Liu

et al. 2020

Biology of Reproduction

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Ephrins are ligands of Eph receptors (Ephs); both of which are sorted into two classes, A and B. There are five types of ephrin-As (ephrin-A1–5) and three types of ephrin-Bs (ephrin-B1–3). Also, there are ten types of EphAs (EphA1–10) and six types of EphBs (EphB1–6). Binding of ephrins to the Eph receptors activates signaling cascades that regulate several biological processes such as cellular proliferation, differentiation, migration, angiogenesis and vascular remodeling. Clarification of their roles in the female reproductive system is crucial to understanding the physiology and pathology of this system. Such knowledge will also create awareness regarding the importance of these molecules in diagnostic, prognostic and therapeutic medicine. Hence, we have discussed the involvement of these molecules in the physiological and pathological events that occur within the female reproductive system. The evidence so far suggests that the ephrins and the Eph receptors modulate folliculogenesis, ovulation, embryo transport, implantation and placentation. Abnormal expression of some of these molecules is associated with PCOS, ovarian cancer, tubal pregnancy, endometrial cancer, uterine leiomyoma (fibroids), cervical cancer and preeclampsia, suggesting the need to utilize these molecules in the clinical setting. To enhance a quick development of this gradually emerging field in female reproductive medicine, we have highlighted some “gaps in knowledge” that need prospective investigation.

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Dysregulated erythropoietin-producing hepatocellular receptor A2 (EphA2) is involved in tubal pregnancy via regulating cell adhesion of the Fallopian tube epithelial cells

Cited by 3 publications

References 34 publications

Interaction networks between the Fallopian tubes and the embryo in human tubal pregnancy: Current knowledge and perspectives

Interaction networks between the Fallopian tubes and the embryo in human tubal pregnancy: Current knowledge and perspectives

Identification of potent pan-ephrin receptor kinase inhibitors using DNA-encoded chemistry technology

Ephrin and Eph receptor signaling in female reproductive physiology and pathology†

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