Buscar

Estamos realizando la búsqueda. Por favor, espere...

 Detalle_Publicacion

Nuclear DICKKOPF-1 as a biomarker of chemoresistance and poor clinical outcome in colorectal cancer

Abstract: Sporadic colorectal cancer (CRC) insurgence and progression depend on the activation of Wnt/ß-catenin signaling. Dickkopf (DKK)-1 is an extracellular inhibitor of Wnt/ß-catenin signaling that also has undefined ß-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

Otras publicaciones de la misma revista o congreso con autores/as de la Universidad de Cantabria

 Fuente: Oncotarget. 2015 Mar 20;6(8):5903-17

Editorial: Impact Journals

 Año de publicación: 2015

Nº de páginas: 14

Tipo de publicación: Artículo de Revista

ISSN: 1949-2553

Proyecto español: SAF2013-43468-R, A.M.; BFU2010-19659, J.M.G-S.; SAF2010-19256, B.J.; SAF2011-23089, C.L-O.

Autores/as

AGUILERA, OSCAR

GONZÁLEZ SANCHO, JOSÉ MANUEL

SAZO, SANDRA

RINCÓN, RAÚL

FERNÁNDEZ, AGUSTÍN F

OLGA TAPIA MARTINEZ

CANALS, FRANCESC

MORTE, BEATRIZ

CALVANESE, VICENZO

ORGAZ, JOSÉ L

NIELL, NÚRIA

AGUILAR, SUSANA

FREIJE, JOSÉ M

GRAÑA, OSVALDO

PISANO, DAVID G

BORRERO, AUREA

MARTÍNEZ USEROS, JAVIER

JIMÉNEZ, BENILDE

FRAGA, MARIO F

GARCÍA FONCILLAS, JESÚS

LÓPEZ OTÍN, CARLOS

MIGUEL ANGEL LAFARGA COSCOJUELA

ROJO, FEDERICO

MUÑOZ, ALBERTO