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dc.provenanceCONICET-
dc.creatorRamakrishnan, Swathi-
dc.creatorHu, Qiang-
dc.creatorKrishnan, Nithya-
dc.creatorWang, Dan-
dc.creatorSmit, Evelyn-
dc.creatorGranger, Victoria-
dc.creatorRak, Monika-
dc.creatorAttwood, Kristopher-
dc.creatorJohnson, Candace-
dc.creatorMorrison, Carl-
dc.creatorPili, Roberto-
dc.creatorChatta, Gurkamal-
dc.creatorGuru, Khurshid-
dc.creatorGueron, Geraldine-
dc.creatorMcNally, Lacey-
dc.creatorWang, Jianmin-
dc.creatorWoloszynska-Read, Anna-
dc.date2018-08-02T18:10:32Z-
dc.date2018-08-02T18:10:32Z-
dc.date2017-12-
dc.date2018-07-11T17:19:56Z-
dc.date.accessioned2019-04-29T15:30:17Z-
dc.date.available2019-04-29T15:30:17Z-
dc.date.issued2017-12-
dc.identifierRamakrishnan, Swathi; Hu, Qiang; Krishnan, Nithya; Wang, Dan; Smit, Evelyn; et al.; Decitabine, a DNA-demethylating agent, promotes differentiation via NOTCH1 signaling and alters immune-related pathways in muscle-invasive bladder cancer; Nature Publishing Group; Cell Death & Disease; 8; 12; 12-2017; 1-13-
dc.identifier2041-4889-
dc.identifierhttp://hdl.handle.net/11336/53915-
dc.identifierCONICET Digital-
dc.identifierCONICET-
dc.identifier.urihttp://rodna.bn.gov.ar:8080/jspui/handle/bnmm/295309-
dc.descriptionAberrant DNA methylation observed in cancer can provide survival benefits to cells by silencing genes essential for anti-tumor activity. DNA-demethylating agents such as Decitabine (DAC)/Azacitidine (AZA) activate otherwise silenced tumor suppressor genes, alter immune response and epigenetically reprogram tumor cells. In this study, we show that non-cytotoxic nanomolar DAC concentrations modify the bladder cancer transcriptome to activate NOTCH1 at the mRNA and protein level, increase double-stranded RNA sensors and CK5-dependent differentiation. Importantly, DAC treatment increases ICN1 expression (the active intracellular domain of NOTCH1) significantly inhibiting cell proliferation and causing changes in cell size inducing morphological alterations reminiscent of senescence. These changes were not associated with β-galactosidase activity or increased p16 levels, but instead were associated with substantial IL-6 release. Increased IL-6 release was observed in both DAC-treated and ICN1 overexpressing cells as compared to control cells. Exogenous IL-6 expression was associated with a similar enlarged cell morphology that was rescued by the addition of a monoclonal antibody against IL-6. Treatment with DAC, overexpression with ICN1 or addition of exogenous IL-6 showed CK5 reduction, a surrogate marker of differentiation. Overall this study suggests that in MIBC cells, DNA hypomethylation increases NOTCH1 expression and IL-6 release to induce CK5-related differentiation.-
dc.descriptionFil: Ramakrishnan, Swathi. Roswell Park Cancer Institute; Estados Unidos-
dc.descriptionFil: Hu, Qiang. Roswell Park Cancer Institute; Estados Unidos-
dc.descriptionFil: Krishnan, Nithya. Roswell Park Cancer Institute; Estados Unidos-
dc.descriptionFil: Wang, Dan. Roswell Park Cancer Institute; Estados Unidos-
dc.descriptionFil: Smit, Evelyn. Roswell Park Cancer Institute; Estados Unidos-
dc.descriptionFil: Granger, Victoria. Roswell Park Cancer Institute; Estados Unidos-
dc.descriptionFil: Rak, Monika. Jagiellonian University; Polonia-
dc.descriptionFil: Attwood, Kristopher. Roswell Park Cancer Institute; Estados Unidos-
dc.descriptionFil: Johnson, Candace. Roswell Park Cancer Institute; Estados Unidos-
dc.descriptionFil: Morrison, Carl. Roswell Park Cancer Institute; Estados Unidos-
dc.descriptionFil: Pili, Roberto. Indiana University; Estados Unidos-
dc.descriptionFil: Chatta, Gurkamal. Roswell Park Cancer Institute; Estados Unidos-
dc.descriptionFil: Guru, Khurshid. Roswell Park Cancer Institute; Estados Unidos-
dc.descriptionFil: Gueron, Geraldine. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina-
dc.descriptionFil: McNally, Lacey. University of Louisville; Estados Unidos-
dc.descriptionFil: Wang, Jianmin. Roswell Park Cancer Institute; Estados Unidos-
dc.descriptionFil: Woloszynska-Read, Anna. Roswell Park Cancer Institute; Estados Unidos-
dc.formatapplication/pdf-
dc.formatapplication/pdf-
dc.languageeng-
dc.publisherNature Publishing Group-
dc.relationinfo:eu-repo/semantics/altIdentifier/doi/https://dx.doi.org/10.1038/s41419-017-0024-5-
dc.relationinfo:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41419-017-0024-5-
dc.rightsinfo:eu-repo/semantics/openAccess-
dc.rightshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/-
dc.sourcereponame:CONICET Digital (CONICET)-
dc.sourceinstname:Consejo Nacional de Investigaciones Científicas y Técnicas-
dc.sourceinstacron:CONICET-
dc.source.urihttp://hdl.handle.net/11336/53915-
dc.subjectdecitabine-
dc.subjectDNA methylation-
dc.subjectNOTCH1-
dc.subjectcancer-
dc.subjectInmunología-
dc.subjectMedicina Básica-
dc.subjectCIENCIAS MÉDICAS Y DE LA SALUD-
dc.titleDecitabine, a DNA-demethylating agent, promotes differentiation via NOTCH1 signaling and alters immune-related pathways in muscle-invasive bladder cancer-
dc.typeinfo:eu-repo/semantics/article-
dc.typeinfo:eu-repo/semantics/publishedVersion-
dc.typeinfo:ar-repo/semantics/articulo-
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