Examinando por Autor "Guerrero, Santiago"

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UNR/CDSE1 expression as prognosis biomarker in resectable pancreatic ductal adenocarcinoma patients: A proof-of-concept
(PLOS, 2017-08-01) Martinez-Useros, Javier; Georgiev-Hristov, Tihomir; Fernández-Aceñero, María Jesús; Borrero-Palacios, Aurea; Indacochea, Alberto; Guerrero, Santiago; Li, Weiyao; Cebrian, Arancha; Gomez del Pulgar, Teresa; Puime-Otin, Alberto; del Puerto-Nevado, Laura; Rodríguez-Remírez, Maria; Perez, Nuria; Celdrán, Ángel; Gebauer, Fatima; García-Foncillas, Jesus
Pancreatic ductal adenocarcinoma is an aggressive form of pancreatic cancer and the fourth leading cause of cancer-related death. When possible, curative approaches are based on surgical resection, though not every patient is a candidate for surgery. There are clinical guidelines for the management of these patients that offer different treatment options depending on the clinical and pathologic characteristics. However, the survival rates seen in this kind of patients are still low. The CDSE1 gene is located upstream of NRAS and encodes an RNA-binding protein termed UNR. The aim of this study was to analyze UNR expression and its correlation with outcome in patients with resectable pancreatic ductal adenocarcinoma (PDAC). For this, samples from resectable PDAC patients who underwent duodenopancreatectomy were used to evaluate UNR protein expression by immunohistochemistry using a tissue microarray. Here, we observed that low UNR expression was significantly associated with shorter progression-free survival after surgery (P = 0.010). Moreover, this prognostic marker remained significant after Cox proportional hazards model (P = 0.036). We further studied the role of CDSE1 expression in patient's prognosis using data from public repositories (GEO and TGCA), confirming our results. Interestingly, CDSE1 expression correlated with that of genes characteristic of an immunogenic molecular subtype of pancreatic cancer. Based on these findings, UNR may be considered a potential prognostic biomarker for resectable PDAC and may serve to guide subsequent adjuvant treatment decisions.
UNR/CSDE1 Drives a Post-transcriptional Program to Promote Melanoma Invasion and Metastasis
(CellPress, 2016-11-14) Wurth, Laurence; Papasaikas, Panagiotis; Olmeda, David; Bley, Nadine; Calvo, Guadalupe T.; Guerrero, Santiago; Cerezo-Wallis, Daniela; Martinez-Useros, Javier; García-Fernández, Maria; Hüttelmaier, Stefan; Soengas, Marisol; Gebauer, Fatima
RNA binding proteins (RBPs) modulate cancer progression through poorly understood mechanisms. Here we show that the RBP UNR/CSDE1 is overexpressed in melanoma tumors and promotes invasion and metastasis. iCLIP sequencing, RNA sequencing, and ribosome profiling combined with in silico studies unveiled sets of pro-metastatic factors coordinately regulated by UNR as part of RNA regulons. In addition to RNA steady-state levels, UNR was found to control many of its targets at the level of translation elongation/termination. Key pro-oncogenic targets of UNR included VIM and RAC1, as validated by loss- and gain-of-function studies. Our results identify UNR as an oncogenic modulator of melanoma progression, unravel the underlying molecular mechanisms, and identify potential targets for this therapeutically challenging malignancy