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Pancreatic Neoplasms: HELP
Articles by Enrique Carrillo-de Santa Pau
Based on 4 articles published since 2009
(Why 4 articles?)
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Between 2009 and 2019, Enrique Carrillo-de-Santa-Pau wrote the following 4 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Article c-Myc downregulation is required for preacinar to acinar maturation and pancreatic homeostasis. 2018

Sánchez-Arévalo Lobo, Victor J / Fernández, Luis César / Carrillo-de-Santa-Pau, Enrique / Richart, Laia / Cobo, Isidoro / Cendrowski, Jaroslaw / Moreno, Ulisses / Del Pozo, Natalia / Megías, Diego / Bréant, Bernardette / Wright, Christopher V / Magnuson, Mark / Real, Francisco X. ·Epithelial Carcinogenesis Group, Cancer Cell Biology Programme, Spanish National Cancer Research Center-CNIO, Madrid, Spain. · Confocal Microscopy Unit, Biotechnology Programme, Spanish National Cancer Research Center-CNIO, Madrid, Spain. · Centre de Recherche des Cordeliers, INSERM, Paris, France. · Department of Cell & Developmental Biology, Vanderbilt Center for Stem Cell Biology, Vanderbilt University, Nashville, Tennessee, USA. · Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain. ·Gut · Pubmed #28159836.

ABSTRACT: BACKGROUND AND AIMS: c-Myc is highly expressed in pancreatic multipotent progenitor cells (MPC) and in pancreatic cancer. The transition from MPC to unipotent acinar progenitors is associated with c-Myc downregulation; a role for c-Myc in this process, and its possible relationship to a role in cancer, has not been established. DESIGN: Using coimmunoprecipitation assays, we demonstrate that c-Myc and Ptf1a interact. Using reverse transcriptase qPCR, western blot and immunofluorescence, we show the erosion of the acinar programme. To analyse the genomic distribution of c-Myc and Ptf1a and the global transcriptomic profile, we used ChIP-seq and RNA-seq, respectively; validation was performed with ChIP-qPCR and RT-qPCR. Lineage-tracing experiments were used to follow the effect of c-Myc overexpression in preacinar cells on acinar differentiation. RESULTS: c-Myc binds and represses the transcriptional activity of Ptf1a CONCLUSIONS: c-Myc repression during development is crucial for the maturation of preacinar cells, and c-Myc overexpression can contribute to pancreatic carcinogenesis through the induction of a dedifferentiated state.

2 Article GATA6 regulates EMT and tumour dissemination, and is a marker of response to adjuvant chemotherapy in pancreatic cancer. 2017

Martinelli, Paola / Carrillo-de Santa Pau, Enrique / Cox, Trevor / Sainz, Bruno / Dusetti, Nelson / Greenhalf, William / Rinaldi, Lorenzo / Costello, Eithne / Ghaneh, Paula / Malats, Núria / Büchler, Markus / Pajic, Marina / Biankin, Andrew V / Iovanna, Juan / Neoptolemos, John / Real, Francisco X. ·Epithelial Carcinogenesis Group, Spanish National Cancer Research Center-CNIO, Madrid, Spain. · Cancer Progression and Metastasis Group, Institute for Cancer Research, Medical University Wien, Vienna, Austria. · Cancer Research UK Liverpool Clinical Trials Unit, University of Liverpool, Liverpool, UK. · NIHR Liverpool Pancreas Biomedical Research Unit, Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK. · Department of Preventive Medicine, Public Health and Microbiology, Universidad Autónoma de Madrid, Madrid, Spain. · Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, Marseille, France. · Institute for Research in Biomedicine (IRB), Barcelona, Spain. · Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center-CNIO, Madrid, Spain. · Department for General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany. · Cancer Division, The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, Australia. · Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK. · West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, UK. · South Western Sydney Clinical School, Faculty of Medicine, University of NSW, Liverpool, Australia. · Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain. ·Gut · Pubmed #27325420.

ABSTRACT: BACKGROUND AND AIMS: The role of GATA factors in cancer has gained increasing attention recently, but the function of GATA6 in pancreatic ductal adenocarcinoma (PDAC) is controversial. GATA6 is amplified in a subset of tumours and was proposed to be oncogenic, but high GATA6 levels are found in well-differentiated tumours and are associated with better patient outcome. By contrast, a tumour-suppressive function of GATA6 was demonstrated using genetic mouse models. We aimed at clarifying GATA6 function in PDAC. DESIGN: We combined GATA6 silencing and overexpression in PDAC cell lines with GATA6 ChIP-Seq and RNA-Seq data, in order to understand the mechanism of GATA6 functions. We then confirmed some of our observations in primary patient samples, some of which were included in the ESPAC-3 randomised clinical trial for adjuvant therapy. RESULTS: GATA6 inhibits the epithelial-mesenchymal transition (EMT) in vitro and cell dissemination in vivo. GATA6 has a unique proepithelial and antimesenchymal function, and its transcriptional regulation is direct and implies, indirectly, the regulation of other transcription factors involved in EMT. GATA6 is lost in tumours, in association with altered differentiation and the acquisition of a basal-like molecular phenotype, consistent with an epithelial-to-epithelial (ET CONCLUSIONS: We provide mechanistic insight into GATA6 tumour-suppressive function, its role as a regulator of canonical epithelial differentiation, and propose that loss of GATA6 expression is both prognostic and predictive of response to adjuvant therapy.

3 Article Choline Kinase Alpha (CHKα) as a Therapeutic Target in Pancreatic Ductal Adenocarcinoma: Expression, Predictive Value, and Sensitivity to Inhibitors. 2016

Mazarico, José M / Sánchez-Arévalo Lobo, Victor J / Favicchio, Rosy / Greenhalf, William / Costello, Eithne / Carrillo-de Santa Pau, Enrique / Marqués, Miriam / Lacal, Juan C / Aboagye, Eric / Real, Francisco X. ·Epithelial Carcinogenesis Group, Cancer Cell Biology Programme, Spanish National Cancer Research Center-CNIO, Madrid, Spain. · Epithelial Carcinogenesis Group, Cancer Cell Biology Programme, Spanish National Cancer Research Center-CNIO, Madrid, Spain. preal@cnio.es vjsanchez@cnio.es. · Comprehensive Cancer Imaging Centre, Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, London, United Kingdom. · The NIHR Liverpool Pancreas Biomedical Research Unit, Liverpool, United Kingdom. · Division of Translational Oncology, Department of Oncology, Fundación Jiménez Díaz, Madrid, Spain. · Epithelial Carcinogenesis Group, Cancer Cell Biology Programme, Spanish National Cancer Research Center-CNIO, Madrid, Spain. Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain. preal@cnio.es vjsanchez@cnio.es. ·Mol Cancer Ther · Pubmed #26769123.

ABSTRACT: Choline kinase α (CHKα) plays a crucial role in the regulation of membrane phospholipid synthesis and has oncogenic properties in vitro. We have analyzed the expression of CHKα in cell lines derived from pancreatic ductal adenocarcinoma (PDAC) and have found increased CHKα expression, associated with differentiation. CHKα protein expression was directly correlated with sensitivity to MN58b, a CHKα inhibitor that reduced cell growth through the induction of apoptosis. Accordingly, CHKα knockdown led to reduced drug sensitivity. In addition, we found that gemcitabine-resistant PDAC cells displayed enhanced sensitivity to CHKα inhibition and, in vitro, MN58b had additive or synergistic effects with gemcitabine, 5-fluorouracil, and oxaliplatin, three active drugs in the treatment of PDAC. Using tissue microarrays, CHKα was found to be overexpressed in 90% of pancreatic tumors. While cytoplasmic CHKα did not relate to survival, nuclear CHKα distribution was observed in 43% of samples and was associated with longer survival, especially among patients with well/moderately differentiated tumors. To identify the mechanisms involved in resistance to CHKα inhibitors, we cultured IMIM-PC-2 cells with increasingly higher concentrations of MN58b and isolated a subline with a 30-fold higher IC50. RNA-Seq analysis identified upregulation of ABCB1 and ABCB4 multidrug resistance transporters, and functional studies confirmed that their upregulation is the main mechanism involved in resistance. Overall, our findings support the notion that CHKα inhibition merits further attention as a therapeutic option in patients with PDAC and that expression levels may predict response.

4 Article BPTF is required for c-MYC transcriptional activity and in vivo tumorigenesis. 2016

Richart, Laia / Carrillo-de Santa Pau, Enrique / Río-Machín, Ana / de Andrés, Mónica P / Cigudosa, Juan C / Lobo, Víctor J Sánchez-Arévalo / Real, Francisco X. ·Epithelial Carcinogenesis Group, Cancer Cell Biology Programme, Spanish National Cancer Research Center-CNIO, Madrid 28029, Spain. · Molecular Cytogenetics Group, Human Cancer Genetics Programme, Spanish National Cancer Research Center-CNIO, Madrid 28029, Spain. · Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona 08003, Spain. ·Nat Commun · Pubmed #26729287.

ABSTRACT: c-MYC oncogene is deregulated in most human tumours. Histone marks associated with transcriptionally active genes define high-affinity c-MYC targets. The mechanisms involved in their recognition by c-MYC are unknown. Here we report that c-MYC interacts with BPTF, a core subunit of the NURF chromatin-remodelling complex. BPTF is required for the activation of the full c-MYC transcriptional programme in fibroblasts. BPTF knockdown leads to decreased c-MYC recruitment to DNA and changes in chromatin accessibility. In Bptf-null MEFs, BPTF is necessary for c-MYC-driven proliferation, G1-S progression and replication stress, but not for c-MYC-driven apoptosis. Bioinformatics analyses unveil that BPTF levels correlate positively with c-MYC-driven transcriptional signatures. In vivo, Bptf inactivation in pre-neoplastic pancreatic acinar cells significantly delays tumour development and extends survival. Our findings uncover BPTF as a crucial c-MYC co-factor required for its biological activity and suggest that the BPTF-c-MYC axis is a potential therapeutic target in cancer.