title: Eph- and ephrin-dependent mechanisms in tumor and stem cell dynamics.
abstract: The erythropoietin-producing hepatocellular (Eph) receptors comprise the largest family of receptor tyrosine kinases (RTKs). Initially regarded as axon-guidance and tissue-patterning molecules, Eph receptors have now been attributed with various functions during development, tissue homeostasis, and disease pathogenesis. Their ligands, ephrins, are synthesized as membrane-associated molecules. At least two properties make this signaling system unique: (1) the signal can be simultaneously transduced in the receptor- and the ligand-expressing cell, (2) the signaling outcome through the same molecules can be opposite depending on cellular context. Moreover, shedding of Eph and ephrin ectodomains as well as ligand-dependent and -independent receptor crosstalk with other RTKs, proteases, and adhesion molecules broadens the repertoire of Eph/ephrin functions. These integrated pathways provide plasticity to cell-microenvironment communication in varying tissue contexts. The complex molecular networks and dynamic cellular outcomes connected to the Eph/ephrin signaling in tumor-host communication and stem cell niche are the main focus of this review.
authors.affiliation: Research Programs Unit, Genome-Scale Biology, Biomedicum Helsinki, University of Helsinki, P.O.B. 63, 00014, Helsinki, Finland.
authors.forename: Erika
authors.initials: E
authors.lastname: Gucciardo
authors.forename: Nami
authors.initials: N
authors.lastname: Sugiyama
authors.forename: Kaisa
authors.initials: K
authors.lastname: Lehti
mesh_terms: D016764:Cell Polarity; D036342:Ephrins / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000378:metabolism; D045726:Metalloproteases / Q000378:metabolism; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000378:metabolism*; D036081:Receptors, Eph Family / Q000378:metabolism*; D015398:Signal Transduction; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D036342:Ephrins; D016023:Integrins; D036081:Receptors, Eph Family; D045726:Metalloproteases; D020741:rho GTP-Binding Proteins