Show simple item record

dc.contributor.authorLópez-Grueso, María José
dc.contributor.authorGonzález, Raúl
dc.contributor.authorMuntané Relat, Jordi
dc.contributor.authorBárcena, J.A.
dc.contributor.authorPadilla, Alicia
dc.date.accessioned2019-10-23T11:00:31Z
dc.date.available2019-10-23T11:00:31Z
dc.date.issued2019
dc.identifier.urihttp://hdl.handle.net/10396/19042
dc.description.abstractSorafenib is the first-line recommended therapy for patients with advanced hepatocarcinoma (HCC) in de-differentiation stage (presenting epithelial–mesenchymal transition, EMT). We studied the role of the thioredoxin system (Trx1/TrxR1) in the sensitivity or resistance of HCC cells to the treatment with Sorafenib. As a model, we used a set of three established HCC cell lines with different degrees of de-differentiation as occurs in metastasis. By quantitative proteomics, we found that the expression levels of Trx1 and TrxR1 followed the same trend as canonical EMT markers in these cell lines. Treatment with Sorafenib induced thiol redox reductive changes in critical elements of oncogenic pathways in all three cell lines but induced drastic proteome reprograming only in HCC cell lines of intermediate stage. Trx1 downregulation counteracted the thiol reductive effect of Sorafenib on Signal Transducer and Activator of Transcription 3 (STAT3) but not on Mitogen-Activated Protein Kinase (MAPK) or Protein Kinase B (Akt) and transformed advanced HCC cells into Sorafenib-sensitive cells. Ten targets of the combined Sorafenib–siRNATrx1 treatment were identified that showed a gradually changing expression trend in parallel to changes in the expression of canonical EMT markers, likely as a result of the activation of Hippo signaling. These findings support the idea that a combination of Sorafenib with thioredoxin inhibitors should be taken into account in the design of therapies against advanced HCC.es_ES
dc.format.mimetypeapplication/pdfes_ES
dc.language.isoenges_ES
dc.publisherMDPIes_ES
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/4.0/es_ES
dc.sourceAntioxidants 8(10), 501 (2019)es_ES
dc.subjectHepatocarcinomaes_ES
dc.subjectThioredoxines_ES
dc.subjectSorafenibes_ES
dc.subjectRedox signalinges_ES
dc.subjectEMTes_ES
dc.titleThioredoxin Downregulation Enhances Sorafenib Effects in Hepatocarcinoma Cellses_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.relation.publisherversionhttp://dx.doi.org/10.3390/antiox8100501es_ES
dc.relation.projectIDGobierno de España. BFU2016-80006-Pes_ES
dc.relation.projectIDInstituto de Salud Carlos III. PI13/00021es_ES
dc.relation.projectIDInstituto de Salud Carlos III. PI16/00090es_ES
dc.relation.projectIDJunta de Andalucía. BIO-0216es_ES
dc.relation.projectIDJunta de Andalucía. CTS-6264es_ES
dc.relation.projectIDJunta de Andalucía. PI-00025-2013es_ES
dc.relation.projectIDJunta de Andalucía. PI-0198-2016es_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record