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dc.contributor.authorSalvestrini, Valentina
dc.contributor.authorCiciarello, Marilena
dc.contributor.authorPensato, Valentina
dc.contributor.authorSimonetti, Giorgia
dc.contributor.authorLaginestra, Maria Antonella
dc.contributor.authorBruno, Samantha
dc.contributor.authorPazzaglia, Martina
dc.contributor.authorDe Marchi, Elena
dc.contributor.authorForte, Dorian
dc.contributor.authorOrecchioni, Stefania
dc.contributor.authorMartinelli, Giovanni
dc.contributor.authorBertolini, Francesco
dc.contributor.authorMendez-Ferrer, Simon 
dc.contributor.authorAdinolfi, Elena
dc.contributor.authorDi Virgilio, Francesco
dc.contributor.authorCavo, Michele
dc.contributor.authorCurti, Antonio
dc.date.accessioned2021-01-08T08:54:52Z
dc.date.available2021-01-08T08:54:52Z
dc.date.issued2020-07-24
dc.identifier.citationFront Oncol. 2020; 10:1225es_ES
dc.identifier.issn2234-943X
dc.identifier.urihttp://hdl.handle.net/20.500.12105/11584
dc.description.abstractThe contribution of cell-extrinsic factors in Acute Myeloid Leukemia (AML) generation and persistence has gained interest. Bitter taste receptors (TAS2Rs) are G protein-coupled receptors known for their primary role as a central warning signal to induce aversion toward noxious or harmful substances. Nevertheless, the increasing amount of evidence about their extra-oral localization has suggested a wider function in sensing microenvironment, also in cancer settings. In this study, we found that AML cells express functional TAS2Rs. We also highlighted a significant association between the modulation of some TAS2Rs and the poor-prognosis AML groups, i.e., TP53- and TET2-mutated, supporting a potential role of TAS2Rs in AML cell biology. Gene expression profile analysis showed that TAS2R activation with the prototypical agonist, denatonium benzoate, significantly modulated a number of genes involved in relevant AML cellular processes. Functional assay substantiated molecular data and indicated that denatonium reduced AML cell proliferation by inducing cell cycle arrest in G0/G1 phase or induced apoptosis via caspase cascade activation. Moreover, denatonium exposure impaired AML cell motility and migratory capacity, and inhibited cellular respiration by decreasing glucose uptake and oxidative phosphorylation. In conclusion, our results in AML cells expand the observation of cancer TAS2R expression to the setting of hematological neoplasms and shed light on a role of TAS2Rs in the extrinsic regulation of leukemia cell functions.es_ES
dc.description.sponsorship: This research was supported by: Bologna AIL (Associazione Italiana contro le Leucemie)/Bologna Brancch, FATRO/Foundation Corrado and Bruno Maria Zaini-Bologna, Fabbri1905, Regione Emilia-Romagna and University of Bologna (Young Researcher's fund of the Regione Emilia Romagna, Bando Alessandro Liberati GREREMAT-Curti to AC), Italian Association for Cancer Research grant (AIRC) IG20109 to FB. VS and MC were supported by the American Society of Haematology (ASH)/Giuseppe Bigi Memorial Award and by the University of Bologna (Alma Idea Junior Grant 2017), EA was supported by AIRC IG16812. DF was supported by AIRC fellowship for abroad-2017, Società Italiana di Ematologia (SIE) and Associazione Amici di Beat Leukemia Dr. Alessandro Cevenini ONLUSes_ES
dc.language.isoenges_ES
dc.publisherFrontiers Media es_ES
dc.type.hasVersionVoRes_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.titleDenatonium as a Bitter Taste Receptor Agonist Modifies Transcriptomic Profile and Functions of Acute Myeloid Leukemia Cells.es_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID32793492es_ES
dc.format.volume10es_ES
dc.format.page1225es_ES
dc.identifier.doi10.3389/fonc.2020.01225es_ES
dc.contributor.funderAssociazione Italiana Contro le Leucemie Linfomi e Mieloma 
dc.contributor.funderFatro Ibérica, S.L. 
dc.contributor.funderFabbri1905 
dc.contributor.funderRegione Emilia-Romagna
dc.contributor.funderUniversity of Bologna (Italia) 
dc.contributor.funderItalian Association for Cancer Research 
dc.contributor.funderAmerican Society of Hematology 
dc.contributor.funderSocietà Italiana di Ematologia 
dc.contributor.funderAssociazione Amici di Beat Leukemia Dr. Alessandro Cevenini ONLUS 
dc.contributor.funderBologna Brancch
dc.contributor.funderFondazione Corrado e Bruno Maria Zaini 
dc.contributor.funderGiuseppe Bigi Memorial Award
dc.description.peerreviewedes_ES
dc.relation.publisherversionhttps://doi.org/10.3389/fonc.2020.01225es_ES
dc.identifier.journalFrontiers in oncologyes_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Antiguos CNICes_ES
dc.repisalud.institucionCNICes_ES
dc.rights.accessRightsopen accesses_ES


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Atribución 4.0 Internacional
Este Item está sujeto a una licencia Creative Commons: Atribución 4.0 Internacional