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dc.contributor.advisorGrandes Moreno, Pedro Rolando ORCID
dc.contributor.advisorWoodhoo, Ashwin
dc.contributor.authorPalomo Irigoyen, Marta
dc.date.accessioned2021-01-21T07:08:55Z
dc.date.available2021-01-21T07:08:55Z
dc.date.issued2020-06-24
dc.date.submitted2020-06-24
dc.identifier.urihttp://hdl.handle.net/10810/49819
dc.description222 p.es_ES
dc.description.abstractCancer cells can develop a strong addiction to discrete molecular regulators, which control the aberranttranscription programs that drive and maintain the cancer phenotype. Here, we report the identificationof the RNA-binding protein HuR as a central oncogenic driver for malignant peripheral nerve sheathtumours (MPNSTs), which are highly aggressive sarcomas. We show HuR was bound to a multitude ofcancer-associated transcripts in human MPNST samples. Accordingly, genetic and pharmacologicalinhibition of HuR had potent cytostatic and cytotoxic effects on tumour growth, and strongly supressedmetastatic capacity in vivo. Importantly, we linked the profound tumorigenic function of HuR to itsability to simultaneously regulate multiple essential oncogenic pathways in MPNST cellls, including theWnt/ß-Catenin, YAP/TAZ, Rb-E2F and BET proteins, which converge on key transcriptional networks.Regulating survival, proliferation, and dissemination. Therefore, we propose HuR represents an idealtherapeutic target for MPNST treatment. Peripheral nervous system involvement has also beenobserved in Lyme disease-assicated clinical manifestations, which is the most common arthropod-borne infectious disease in temperate regions. It is caused by infection with the spirochete Borreliaburgdorferi, which is transmitted by a tick bite. Here, we identified Schwann cells as the new targets ofB. burgdorferi, leading to demyelination in the absence of immune cells. We suggest that B. burgdorferiregulates intracellular signaling pathways, including Wnt/ß-Catenin, to strongly repress myelin gene andprotein expression, throwing light on one of the most intriguing pathological features of Lyme disease.es_ES
dc.description.sponsorshipCICbioGUNEes_ES
dc.language.isoenges_ES
dc.rightsinfo:eu-repo/semantics/openAccesses_ES
dc.subjectneurophysiologyes_ES
dc.subjectneurochemistryes_ES
dc.subjectneurofisiologíaes_ES
dc.subjectneuroquímicaes_ES
dc.titleGene Regulatory Network in Schwann cell Disorderses_ES
dc.typeinfo:eu-repo/semantics/doctoralThesises_ES
dc.rights.holder(c)2020 MARTA PALOMO IRIGOYEN
dc.identifier.studentID602635es_ES
dc.identifier.projectID17809es_ES
dc.departamentoesNeurocienciases_ES
dc.departamentoeuNeurozientziakes_ES


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