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Stimulatory actions of IGF-I are mediated by IGF-IR cross-talk with GPER and DDR1 in mesothelioma and lung cancer cells

dc.contributor.authorAvino, Silvia
dc.contributor.authorAndò, Sebastiano
dc.contributor.authorMaggiolini, Marcello
dc.date.accessioned2020-10-12T16:09:46Z
dc.date.available2020-10-12T16:09:46Z
dc.date.issued2017-06-12
dc.identifier.urihttp://hdl.handle.net/10955/5328
dc.identifier.urihttps://doi.org/10.13126/unical.it/dottorati/5328
dc.descriptionDottorato di Ricerca in Medicina Traslazionale. Ciclo XXIXen_US
dc.description.abstractInsulin-like growth factor-I (IGF-I)/IGF-I receptor (IGF-IR) system has been largely involved in the pathogenesis and development of various tumors. We have previously demonstrated that IGF-IR cooperates with the G-protein estrogen receptor (GPER) and the collagen receptor discoidin domain 1 (DDR1) that are implicated in cancer progression. Here, we provide novel evidence regarding the molecular mechanisms through which IGF-I/IGF-IR signaling triggers a functional cross-talk with GPER and DDR1 in both mesothelioma and lung cancer cells. In particular, we show that IGF-I activates the transduction network mediated by IGF-IR leading to the up-regulation of GPER and its main target genes CTGF and EGR1 as well as the induction of DDR1 target genes like MATN-2, FBN-1, NOTCH 1 and HES-1. Of note, certain DDR1-mediated effects upon IGF-I stimulation required both IGF-IR and GPER as determined knocking-down the expression of these receptors. The aforementioned findings were nicely recapitulated in important biological outcomes like IGFI promoted chemotaxis and migration of both mesothelioma and lung cancer cells. Overall, our data suggest that IGF-I/IGF-IR system triggers stimulatory actions through both GPER and DDR1 in aggressive tumors as mesothelioma and lung tumors. Hence, this novel signaling pathway may represent a further target in setting innovative anticancer strategiesen_US
dc.description.sponsorshipUniversità della Calabriaen_US
dc.language.isoenen_US
dc.relation.ispartofseriesMED/04;
dc.subjectInsulin-like growth factoren_US
dc.subjectMesotheliomaen_US
dc.titleStimulatory actions of IGF-I are mediated by IGF-IR cross-talk with GPER and DDR1 in mesothelioma and lung cancer cellsen_US
dc.typeThesisen_US


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