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dc.contributor.authorAguilera, Óscar
dc.contributor.authorGonzález Sancho, José Manuel
dc.contributor.authorZazo Hernández, Sandra
dc.contributor.authorRincón, Raúl
dc.contributor.authorFernández Fernández, Agustín
dc.contributor.authorTapia Martínez, Olga
dc.contributor.authorCanals, Francesc
dc.contributor.authorMorte Molina, Beatriz
dc.contributor.authorCalvanese, Vincenzo
dc.contributor.authorOrgaz Bueno, José Luis
dc.contributor.authorNiell Garolera, Núria
dc.contributor.authorAguilar, Susana
dc.contributor.authorFreije, José M.
dc.contributor.authorGraña, Osvaldo
dc.contributor.authorPisano, David G.
dc.contributor.authorBorrero Palacios, Aurea
dc.contributor.authorMartínez Useros, Javier
dc.contributor.authorJiménez Cuenca, Benilde
dc.contributor.authorFernández Fraga, Mario
dc.contributor.authorGarcía Foncillas, Jesús
dc.contributor.authorLópez Otín, Carlos
dc.contributor.authorLafarga Coscojuela, Miguel Ángel 
dc.contributor.authorRojo, Federico
dc.contributor.authorMuñoz Terol, Alberto
dc.contributor.otherUniversidad de Cantabriaes_ES
dc.description.abstractSporadic colorectal cancer (CRC) insurgence and progression depend on the activation of Wnt/β-catenin signaling. Dickkopf (DKK)-1 is an extracellular inhibitor of Wnt/β-catenin signaling that also has undefined β-catenin-independent actions. Here we report for the first time that a proportion of DKK-1 locates within the nucleus of healthy small intestine and colon mucosa, and of CRC cells at specific chromatin sites of active transcription. Moreover, we show that DKK-1 regulates several cancer-related genes including the cancer stem cell marker aldehyde dehydrogenase 1A1 (ALDH1A1) and Ral-binding protein 1-associated Eps domain-containing 2 (REPS2), which are involved in detoxification of chemotherapeutic agents. Nuclear DKK-1 expression is lost along CRC progression; however, it remains high in a subset (15%) of CRC patients (n = 699) and associates with decreased progression-free survival (PFS) after chemotherapy administration and overall survival (OS) [adjusted HR, 1.65; 95% confidence interval (CI), 1.23-2.21; P = 0.002)]. Overexpression of ALDH1A1 and REPS2 associates with nuclear DKK-1 expression in tumors and correlates with decreased OS (P = 0.001 and 0.014) and PFS. In summary, our findings demonstrate a novel location of DKK-1 within the cell nucleus and support a role of nuclear DKK-1 as a predictive biomarker of chemoresistance in colorectal cancer.es_ES
dc.format.extent15 p.es_ES
dc.publisherImpact Journalses_ES
dc.rightsAtribución 3.0 España*
dc.sourceOncotarget. 2015 Mar 20;6(8):5903-17es_ES
dc.subject.otherColorectal canceres_ES
dc.titleNuclear DICKKOPF-1 as a biomarker of chemoresistance and poor clinical outcome in colorectal canceres_ES

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Atribución 3.0 EspañaExcept where otherwise noted, this item's license is described as Atribución 3.0 España