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dc.contributor.authorNàger Grifo, Mireia
dc.contributor.authorCrespí Sallán, Marta
dc.contributor.authorVisa Pretel, Anna
dc.contributor.authorPushparaj, Charumathi
dc.contributor.authorSantacana Espasa, Maria
dc.contributor.authorMacià Armengol, Anna
dc.contributor.authorYeramian Hakim, Andree
dc.contributor.authorCantí Nicolás, Carles
dc.contributor.authorHerreros Danés, Judit
dc.date.accessioned2018-02-14T09:21:01Z
dc.date.available2019-01-09T23:29:18Z
dc.date.issued2018-01-09
dc.identifier.issn1554-8627
dc.identifier.urihttp://hdl.handle.net/10459.1/62654
dc.description.abstractWNT-CTNN1B signaling promotes cancer cell proliferation and stemness. Furthermore, recent evidence indicates that macroautophagy/autophagy regulates WNT signaling. Here we investigated the impact of inhibiting WNT signaling on autophagy in glioblastoma (GBM), a devastating brain tumor. Inhibiting TCF, or silencing TCF4 or CTNNB1/β-catenin upregulated SQSTM1/p62 in GBM at transcriptional and protein levels and, in turn, autophagy. DKK1/Dickkopf1, a canonical WNT receptor antagonist, also induced autophagic flux. Importantly, TCF inhibition regulated autophagy through MTOR inhibition and dephosphorylation, and nuclear translocation of TFEB, a master regulator of lysosomal biogenesis and autophagy. TCF inhibition or silencing additionally affected GBM cell proliferation and migration. Autophagy induction followed by its blockade can promote cancer cell death. In agreement with this notion, halting both TCF-CTNNB1 and autophagy pathways decreased cell viability and induced apoptosis of GBM cells through a SQSTM1-dependent mechanism involving CASP8 (caspase 8). In vivo experiments further underline the therapeutic potential of such dual targeting in GBM.
dc.format.mimetypeapplication/pdf
dc.language.isoeng
dc.publisherTaylor & Francis
dc.relation.isformatofReproducció del document publicat a https://doi.org/10.1080/15548627.2017.1423439
dc.relation.ispartofAutophagy, 2018, vol. 14, núm. 4, p. 619-636
dc.rights(c) Taylor & Francis, 2018
dc.subject.classificationGlioblastoma multiforme
dc.subject.classificationAutofàgia
dc.subject.otherAutophagy
dc.subject.otherGlioblastoma
dc.subject.otherCTNNB1
dc.subject.otherSQSTM1
dc.titleInhibition of WNT-CTNNB1 signaling upregulates SQSTM1 and sensitizes glioblastoma cells to autophagy blockers
dc.typeinfo:eu-repo/semantics/article
dc.date.updated2018-02-14T09:21:02Z
dc.identifier.idgrec026532
dc.type.versioninfo:eu-repo/semantics/acceptedVersion
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.identifier.doihttps://doi.org/10.1080/15548627.2017.1423439


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