PMID: 25788273Mar 20, 2015Paper

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

Oncotarget
Óscar AguileraA Muñoz

Abstract

Sporadic 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 locatio...Continue Reading

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Citations

Dec 19, 2017·Oncology Letters·Magdalena SzaryńskaZbigniew Kmieć
Jun 3, 2017·British Journal of Pharmacology·Michael H Kagey, Xi He
Jul 2, 2016·Cancers·Mélody MazonMadeleine Carreau
Apr 7, 2020·Cancer Letters·Nikolai JaschkeTilman D Rachner
Jun 8, 2021·Frontiers in Immunology·Hang Yin ChuGe Zhang

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