Eph Receptors And Ephrins In Cancer Bidirectional Signalling And Beyond Pdf

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

This is an open access article distributed under the terms of Creative Commons Attribution License. Few markers, such as receptor tyrosine kinases RTKs from the epidermal growth factor receptor EGFR family, are currently used in clinical practice to estimate patient prognosis or determine the appropriate treatment course. However, some patients continue to develop metastasis, thus indicating the need for novel clinical markers and therapeutic targets. Members of the Eph from the erythropoietin-producing hepatocellular cell line where it was first cloned receptors have been found to be overexpressed in screens of RTKs in cancer 1 , 2. The Eph receptor was first identified in an erythropoietin-producing human hepatocellular carcinoma cell line ETL-1 3 in an effort to discover novel tyrosine kinase receptors. This family now constitutes the largest family of RTKs participating in cell-to-cell communications and tissue integrity during embryogenesis, as well as in cell proliferation, survival and motility, which are crucial steps towards the development of metastases 1 , 4.

Eph receptor protein-tyrosine kinases are among the oldest known animal receptors and have greatly expanded in number during vertebrate evolution. Their complex transduction mechanisms are capable of bidirectional and bimodal multi-response signaling. Eph receptors are expressed in almost every cell type in the human body, yet their roles in development, physiology, and disease are incompletely understood. Studies in C. Here we review advances in our understanding of Eph receptor signaling made using the C. Eph receptors EphRs are the largest subfamily of receptor protein-tyrosine kinases in vertebrates, with fourteen members encoded in the human genome Pasquale, ; Pitulescu and Adams, The name Eph is for Erythropoietin-producing hepatocellular carcinoma cell line from which the first cDNA was isolated Hirai et al.

Eph receptors and ephrins in cancer: bidirectional signalling and beyond

Ephrins also known as ephrin ligands or Eph family receptor interacting proteins are a family of proteins that serve as the ligands of the eph receptor. Eph receptors in turn compose the largest known subfamily of receptor protein-tyrosine kinases RTKs. Ephrin ligands are divided into two subclasses of ephrin-A and ephrin-B based on their structure and linkage to the cell membrane. Ephrin-As are anchored to the membrane by a glycosylphosphatidylinositol GPI linkage and lack a cytoplasmic domain, while ephrin-Bs are attached to the membrane by a single transmembrane domain that contains a short cytoplasmic PDZ-binding motif. Eph receptors in turn are classified as either EphAs or EphBs based on their binding affinity for either the ephrin-A or ephrin-B ligands. Although Eph-ephrin activation is usually associated with decreased growth cone survival and the repulsion of migrating axons, it has recently been demonstrated that growth cone survival does not depend just on Eph-ephrin activation, but rather on the differential effects of "forward" signaling by the Eph receptor or "reverse" signaling by the ephrin ligand on growth cone survival.

Eph Receptor Signaling and Ephrins

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.

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The Eph receptors are the largest of the RTK families. Like other RTKs, they transduce signals from the cell exterior to the interior through ligand-induced activation of their kinase domain. However, the Eph receptors also have distinctive features. Instead of binding soluble ligands, they generally mediate contact-dependent cell—cell communication by interacting with surface-associated ligands—the ephrins—on neighboring cells.

Eph receptors and ephrins in cancer: bidirectional signaling and beyond

Eph erythropoietin-producing hepatoma receptors and Ephrin ligands constitute the largest subfamily of receptor tyrosine kinase RTK , which were first discovered in tumors. Heretofore, Eph protein has been shown to be involved in various tumor biological behaviors including proliferation and progression. The occurrence of specific types of tumor is closely related to the virus infection.

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The Eph receptor tyrosine kinases and their ephrin ligands have intriguing expression patterns in cancer cells and tumor blood vessels, which suggest important roles for their bidirectional signals in multiple aspects of cancer development and progression. Eph gene mutations likely also contribute to cancer pathogenesis. However, Eph signaling activities in cancer appear to be complex, and are characterized by puzzling dichotomies.

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Eph receptors and ephrins in cancer: Bidirectional signalling and beyond The Eph receptor tyrosine kinases and their ephrin ligands have intriguing expression patterns in cancer cells and tumour blood vessels, which suggest important roles for their bidirectional signals in Request Full-text Paper PDF.


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