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The emerging role of mTOR up-regulation in brain astrocytoma

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dc.contributor.authorRyskalin, Larisa
dc.contributor.authorLimanaqi, Fiona
dc.contributor.authorBiagioni, Francesca
dc.contributor.authorFrati, Alessandro
dc.contributor.authorEsposito, Vincenzo
dc.contributor.authorCalierno, Maria Teresa
dc.contributor.authorLenzi, Paola
dc.contributor.authorFornai, Francesco
dc.date.accessioned2022-02-21T07:57:02Z
dc.date.available2022-02-21T07:57:02Z
dc.date.issued2017
dc.description.abstractThe present manuscript is an overview of various effects of mTOR up-regulation in astrocytoma with an emphasis on its deleterious effects on the proliferation of Glioblastoma Multiforme. The manuscript reports consistent evidence indicating the occurrence of mTOR up-regulation both in experimental and human astrocytoma. The grading of human astrocytoma is discussed in relationship with mTOR upregulation. In the second part of the manuscript, the biochemical pathways under the influence of mTOR are translated to cell phenotypes which are generated by mTOR up-regulation and reverted by its inhibition. A special section is dedicated to the prominent role of autophagy in mediating the effects of mTOR in glioblastoma. In detail, autophagy inhibition produced by mTOR up-regulation determines the fate of cancer stem cells. On the other hand, biochemical findings disclose the remarkable effects of autophagy activators as powerful inducers of cell differentiation with a strong prevalence towards neuronal phenotypes. Thus, mTOR modulation acts on the neurobiology of glioblastoma just like it operates in vivo at the level of brain stem cell niches by altering autophagy-dependent cell differentiation. In the light of such a critical role of autophagy we analyzed the ubiquitin proteasome system. The merging between autophagy and proteasome generates a novel organelle, named autophagoproteasome which is strongly induced by mTOR inhibitors in glioblastoma cells. Remarkably, when mTOR is maximally inhibited the proteasome component selectively moves within autophagy vacuoles, thus making the proteasome activity dependent on the entry within autophagy compartment.es
dc.formatapplication/pdfes
dc.format.extent19es
dc.identifier.citationHistology and Histopathology, Vol.32, nÂş5, (2017)
dc.identifier.doiDOI: 10.14670/HH-11-835
dc.identifier.issn1699-5848
dc.identifier.issn0213-3911
dc.identifier.urihttp://hdl.handle.net/10201/117183
dc.languageenges
dc.publisherUniversidad de Murcia. Departamento de BiologĂ­a Celular e HistologĂ­aes
dc.relationSin financiaciĂłn externa a la Universidades
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectAutophagyes
dc.subjectAutophagoproteasomees
dc.subjectCancer stem cellses
dc.subjectGlioblastomaes
dc.subjectStem cell differentiationes
dc.subject.otherCDU::6 - Ciencias aplicadas::61 - Medicina::616 - PatologĂ­a. Medicina clĂ­nica. OncologĂ­aes
dc.titleThe emerging role of mTOR up-regulation in brain astrocytomaes
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
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Histology and histopathology Vol.32, nÂş5 (2017)