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505 results on '"Casal, J. Ignacio"'

1. Metallothionein-3 is a multifunctional driver that modulates the development of sorafenib-resistant phenotype in hepatocellular carcinoma cells

Author

Rodrigo, Miguel Angel Merlos, Michalkova, Hana, Jimenez, Ana Maria Jimenez, Petrlak, Frantisek, Do, Tomas, Sivak, Ladislav, Haddad, Yazan, Kubickova, Petra, de los Rios, Vivian, Casal, J. Ignacio, Serrano-Macia, Marina, Delgado, Teresa C., Boix, Loreto, Bruix, Jordi, Martinez Chantar, Maria L., Adam, Vojtech, and Heger, Zbynek

Published
2024
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4. Integrated meta-analysis of colorectal cancer public proteomic datasets for biomarker discovery and validation

Author

Ministerio de Ciencia e Innovación (España), Comunidad de Madrid, Robles, Javier [0000-0002-8438-5942], Prakash, Ananth [0000-0001-5799-9618], Vizcaíno, Juan Antonio [0000-0002-3905-4335], Casal, J. Ignacio [0000-0003-1085-2840], Robles, Javier, Prakash, Ananth, Vizcaíno, Juan Antonio, Casal, J. Ignacio, Ministerio de Ciencia e Innovación (España), Comunidad de Madrid, Robles, Javier [0000-0002-8438-5942], Prakash, Ananth [0000-0001-5799-9618], Vizcaíno, Juan Antonio [0000-0002-3905-4335], Casal, J. Ignacio [0000-0003-1085-2840], Robles, Javier, Prakash, Ananth, Vizcaíno, Juan Antonio, and Casal, J. Ignacio

Abstract

The cancer biomarker field has been an object of thorough investigation in the last decades. Despite this, colorectal cancer (CRC) heterogeneity makes it challenging to identify and validate effective prognostic biomarkers for patient classification according to outcome and treatment response. Although a massive amount of proteomics data has been deposited in public data repositories, this rich source of information is vastly underused. Here, we attempted to reuse public proteomics datasets with two main objectives: i) to generate hypotheses (detection of biomarkers) for their posterior/downstream validation, and (ii) to validate, using an orthogonal approach, a previously described biomarker panel. Twelve CRC public proteomics datasets (mostly from the PRIDE database) were re-analysed and integrated to create a landscape of protein expression. Samples from both solid and liquid biopsies were included in the reanalysis. Integrating this data with survival annotation data, we have validated in silico a six-gene signature for CRC classification at the protein level, and identified five new blood-detectable biomarkers (CD14, PPIA, MRC2, PRDX1, and TXNDC5) associated with CRC prognosis. The prognostic value of these blood-derived proteins was confirmed using additional public datasets, supporting their potential clinical value. As a conclusion, this proof-of-the-concept study demonstrates the value of re-using public proteomics datasets as the basis to create a useful resource for biomarker discovery and validation. The protein expression data has been made available in the public resource Expression Atlas.

Published
2024

6. Multiplexed Biosensing Diagnostic Platforms Detecting Autoantibodies to Tumor-Associated Antigens from Exosomes Released by CRC Cells and Tissue Samples Showed High Diagnostic Ability for Colorectal Cancer

Author

Montero-Calle, Ana, Aranguren-Abeigon, Itziar, Garranzo-Asensio, María, Poves, Carmen, Fernández-Aceñero, María Jesús, Martínez-Useros, Javier, Sanz, Rodrigo, Dziaková, Jana, Rodriguez-Cobos, Javier, Solís-Fernández, Guillermo, Povedano, Eloy, Gamella, Maria, Torrente-Rodríguez, Rebeca Magnolia, Alonso-Navarro, Miren, de los Ríos, Vivian, Casal, J. Ignacio, Domínguez, Gemma, Guzman-Aranguez, Ana, Peláez-García, Alberto, Pingarrón, José Manuel, Campuzano, Susana, and Barderas, Rodrigo

Published
2021
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9. Proteomic profiling and network biology of colorectal cancer liver metastasis

Author

Ministerio de Ciencia e Innovación (España), Instituto de Salud Carlos III, Bartolomé, Rubén Álvaro [0000-0002-3292-1491], Casal, J. Ignacio [0000-0003-1085-2840], Bartolomé, Rubén Álvaro, Casal, J. Ignacio, Ministerio de Ciencia e Innovación (España), Instituto de Salud Carlos III, Bartolomé, Rubén Álvaro [0000-0002-3292-1491], Casal, J. Ignacio [0000-0003-1085-2840], Bartolomé, Rubén Álvaro, and Casal, J. Ignacio

Abstract

Introduction: Tissue-based proteomic studies of colorectal cancer (CRC) metastasis have delivered fragmented results, with very few therapeutic targets and prognostic biomarkers moving beyond the discovery phase. This situation is likely due to the difficulties in obtaining and analyzing large numbers of patient-derived metastatic samples, the own heterogeneity of CRC, and technical limitations in proteomics discovery. As an alternative, metastatic CRC cell lines provide a flexible framework to investigate the underlying mechanisms and network biology of metastasis for target discovery., Areas Covered: In this perspective, we comment on different in-depth proteomic studies of metastatic versus non-metastatic CRC cell lines. Identified metastasis-related proteins are introduced and discussed according to the spatial location in different cellular fractions, with special emphasis on membrane/adhesion proteins, secreted proteins, and nuclear factors, including miRNAs associated with liver metastasis. Moreover, we analyze the biological significance and potential therapeutic applications of the identified liver metastasis-related proteins., Expert Opinion: The combination of protein discovery and functional analysis is the only way to accelerate the progress to clinical translation of the proteomic-derived findings in a relatively fast pace. Patient-derived organoids represent a promising alternative to patient tissues and cell lines, but further optimizations are still required for achieving solid and reproducible results.

Published
2023

12. A multicentric study to evaluate the use of relative retention times in targeted proteomics

Author

Vialas, Vital, Colomé-Calls, Núria, Abian, Joaquín, Aloria, Kerman, Alvarez-Llamas, Gloria, Antúnez, Oreto, Arizmendi, Jesus M., Azkargorta, Mikel, Barceló-Batllori, Silvia, Barderas, María G., Blanco, Francisco, Casal, J. Ignacio, Casas, Vanessa, de la Torre, Carolina, Chicano-Gálvez, Eduardo, Elortza, Felix, Espadas, Guadalupe, Estanyol, Josep M., Fernandez-Irigoyen, Joaquín, Fernandez-Puente, Patricia, Fidalgo, María José, Fuentes, Manuel, Gay, Marina, Gil, Concha, Hainard, Alexandre, Hernaez, Maria Luisa, Ibarrola, Nieves, Kopylov, Arthur T., Lario, Antonio, Lopez, Juan Antonio, López-Lucendo, María, Marcilla, Miguel, Marina-Ramírez, Anabel, Marko-Varga, Gyorgy, Martín, Luna, Mora, Maria I., Morato-López, Esperanza, Muñoz, Javier, Odena, Maria Antonia, de Oliveira, Eliandre, Orera, Irene, Ortea, Ignacio, Pasquarello, Carla, Ray, Kevin B., Rezeli, Melinda, Ruppen, Isabel, Sabidó, Eduard, del Pino, Manuel M. Sanchez, Sancho, Jaime, Santamaría, Enrique, Vazquez, Jesus, Vilaseca, Marta, Vivanco, Fernando, Walters, James J., Zgoda, Victor G., Corrales, Fernando J., Canals, Francesc, and Paradela, Alberto

Published
2017
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13. Spatial proteomic analysis of isogenic metastatic colorectal cancer cells reveals key dysregulated proteins associated with lymph node, liver, and lung metastasis

Author

Instituto de Salud Carlos III, European Commission, Research Foundation - Flanders, Flemish Government, KU Leuven, Ministerio de Educación, Cultura y Deporte (España), Solís-Fernández, Guillermo [0000-0002-4785-0040], Montero-Calle, Ana [0000-0001-5141-0454], Martínez-Useros, Javier [0000-0001-9007-828X], López-Janeiro, Álvaro [0000-0002-5744-3115], Ríos, Vivian de los [0000-0001-5582-6879], Dziaková, Jana [0000-0001-5317-5275], Molina-Roldán, Elena Milagrosa [0000-0002-8882-8405], Fernandez-Aceñero, M. Jesús [0000-0002-2439-3553], Peláez-García, Alberto [0000-0002-5401-3216], Casal, J. Ignacio [0000-0003-1085-2840], Hofkens, Johan [0000-0002-9101-0567], Rocha, Susana [0000-0003-1258-9396], Barderas, Rodrigo [0000-0003-3539-7469], Solís-Fernández, Guillermo, Montero-Calle, Ana, Martínez-Useros, Javier, López-Janeiro, Álvaro, Ríos, Vivian de los, Sanz, Rodrigo, Dziaková, Jana, Molina-Roldán, Elena Milagrosa, Fernandez-Aceñero, M. Jesús, Peláez-García, Alberto, Casal, J. Ignacio, Hofkens, Johan, Rocha, Susana, Barderas, Rodrigo, Instituto de Salud Carlos III, European Commission, Research Foundation - Flanders, Flemish Government, KU Leuven, Ministerio de Educación, Cultura y Deporte (España), Solís-Fernández, Guillermo [0000-0002-4785-0040], Montero-Calle, Ana [0000-0001-5141-0454], Martínez-Useros, Javier [0000-0001-9007-828X], López-Janeiro, Álvaro [0000-0002-5744-3115], Ríos, Vivian de los [0000-0001-5582-6879], Dziaková, Jana [0000-0001-5317-5275], Molina-Roldán, Elena Milagrosa [0000-0002-8882-8405], Fernandez-Aceñero, M. Jesús [0000-0002-2439-3553], Peláez-García, Alberto [0000-0002-5401-3216], Casal, J. Ignacio [0000-0003-1085-2840], Hofkens, Johan [0000-0002-9101-0567], Rocha, Susana [0000-0003-1258-9396], Barderas, Rodrigo [0000-0003-3539-7469], Solís-Fernández, Guillermo, Montero-Calle, Ana, Martínez-Useros, Javier, López-Janeiro, Álvaro, Ríos, Vivian de los, Sanz, Rodrigo, Dziaková, Jana, Molina-Roldán, Elena Milagrosa, Fernandez-Aceñero, M. Jesús, Peláez-García, Alberto, Casal, J. Ignacio, Hofkens, Johan, Rocha, Susana, and Barderas, Rodrigo

Abstract

Metastasis is the primary cause of colorectal cancer (CRC) death. The liver and lung, besides adjacent lymph nodes, are the most common sites of metastasis. Here, we aimed to study the lymph nodes, liver, and lung CRC metastasis by quantitative spatial proteomics analysis using CRC cell-based models that recapitulate these metastases. The isogenic KM12 cell system composed of the non-metastatic KM12C cells, liver metastatic KM12SM cells, and liver and lung metastatic KM12L4a cells, and the isogenic non-metastatic SW480 and lymph nodes metastatic SW620 cells, were used. Cells were fractionated to study by proteomics five subcellular fractions corresponding to cytoplasm, membrane, nucleus, chromatin-bound proteins, and cytoskeletal proteins, and the secretome. Trypsin digested extracts were labeled with TMT 11-plex and fractionated prior to proteomics analysis on a Q Exactive. We provide data on protein abundance and localization of 4710 proteins in their different subcellular fractions, depicting dysregulation of proteins in abundance and/or localization in the most common sites of CRC metastasis. After bioinformatics, alterations in abundance and localization for selected proteins from diverse subcellular localizations were validated via WB, IF, IHC, and ELISA using CRC cells, patient tissues, and plasma samples. Results supported the relevance of the proteomics results in an actual CRC scenario. It was particularly relevant that the measurement of GLG1 in plasma showed diagnostic ability of advanced stages of the disease, and that the mislocalization of MUC5AC and BAIAP2 in the nucleus and membrane, respectively, was significantly associated with poor prognosis of CRC patients. Our results demonstrate that the analysis of cell extracts dilutes protein alterations in abundance in specific localizations that might only be observed studying specific subcellular fractions, as here observed for BAIAP2, GLG1, PHYHIPL, TNFRSF10A, or CDKN2AIP, which are interesting protein

Published
2022

14. A prognostic six-gene expression risk-score derived from proteomic profiling of the metastatic colorectal cancer secretome

Author

Ministerio de Industria, Comercio y Turismo (España), Comunidad de Madrid, Instituto de Salud Carlos III, Robles, Javier [0000-0002-8438-5942], Pintado-Berninches, Laura [0000-0002-3331-7130], Escudero-Paniagua, B. [0000-0003-3882-5529], Ríos, Vivian de los [0000-0001-5582-6879], Bartolomé, Rubén Álvaro [0000-0002-3292-1491], Jaén, Marta [0000-0002-2088-8807], Martin-Regalado, Ángela [0000-0003-4891-5499], Fernandez-Aceñero, M. Jesús [0000-0002-2439-3553], Imbaud, Juan Ignacio [0000-0002-6026-4265], Casal, J. Ignacio [0000-0003-1085-2840], Robles, Javier, Pintado-Berninches, Laura, Boukich, Issam, Escudero-Paniagua, B., Ríos, Vivian de los, Bartolomé, Rubén Álvaro, Jaén, Marta, Martin-Regalado, Ángela, Fernandez-Aceñero, M. Jesús, Imbaud, Juan Ignacio, Casal, J. Ignacio, Ministerio de Industria, Comercio y Turismo (España), Comunidad de Madrid, Instituto de Salud Carlos III, Robles, Javier [0000-0002-8438-5942], Pintado-Berninches, Laura [0000-0002-3331-7130], Escudero-Paniagua, B. [0000-0003-3882-5529], Ríos, Vivian de los [0000-0001-5582-6879], Bartolomé, Rubén Álvaro [0000-0002-3292-1491], Jaén, Marta [0000-0002-2088-8807], Martin-Regalado, Ángela [0000-0003-4891-5499], Fernandez-Aceñero, M. Jesús [0000-0002-2439-3553], Imbaud, Juan Ignacio [0000-0002-6026-4265], Casal, J. Ignacio [0000-0003-1085-2840], Robles, Javier, Pintado-Berninches, Laura, Boukich, Issam, Escudero-Paniagua, B., Ríos, Vivian de los, Bartolomé, Rubén Álvaro, Jaén, Marta, Martin-Regalado, Ángela, Fernandez-Aceñero, M. Jesús, Imbaud, Juan Ignacio, and Casal, J. Ignacio

Abstract

The necessity to accurately predict recurrence and clinical outcome in early stage colorectal cancer (CRC) is critical to identify those patients who may benefit from adjuvant chemotherapy. Here, we developed and validated a gene-based risk-score algorithm for patient stratification and personalised treatment in early stage disease based on alterations in the secretion of metastasis-related proteins. A quantitative label-free proteomic analysis of the secretome of highly and poorly metastatic CRC cell lines with different genetic backgrounds revealed 153 differentially secreted proteins (fold-change >5). These changes in the secretome were validated at the transcriptomic level. Starting from 119 up-regulated proteins, a six-gene/protein-based prognostic signature composed of IGFBP3, CD109, LTBP1, PSAP, BMP1, and NPC2 was identified after sequential discovery, training,and validation in four different cohorts. This signature was used to develop a risk-score algorithm, named SEC6,for patient stratification. SEC6 risk-score components showed higher expression in the poor prognosis CRC sub types: consensus molecular subtype 4 (CMS4), CRIS-B, and stem-like. High expression of the signature was also associated with patients showing dMMR, CIMP+ status, and BRAF mutations. In addition, the SEC6 signature was associated with lower overall survival, progression-free interval, and disease-specific survival in stage II and III patients. SEC6-based risk stratification indicated that 5-FU treatment was beneficial for low-risk patients,whereas only aggressive treatments (FOLFOX and FOLFIRI) provided benefits to high-risk patients in stages II and III. In summary, this novel risk-score demonstrates the value of the secretome compartment as a reliable source for the retrieval of biomarkers with high prognostic and chemotherapy-predictive capacity, providing a potential new tool for tailoring decision-making in patient care.

Published
2022

15. Multi-laboratory experiment PME11 for the standardization of phosphoproteome analysis

Author

Instituto de Salud Carlos III, Abián, Joaquín [0000-0003-2823-5429], Aloria, Kerman [0000-0001-7268-7700], Arizmendi, Jesús M. [0000-0002-1412-4042], Barceló-Batllori, Silvia [0000-0002-5352-9747], Burlet-Schiltz, Odile [0000-0002-3606-2356], Carrascal, Montserrat [0000-0002-0205-2176], Casal, J. Ignacio [0000-0003-1085-2840], Chicano-Gálvez, Eduardo [0000-0002-9481-9628], Chiva, Cristina [0000-0001-8150-6203], Elortza, Felix [0000-0001-8839-5438], Estanyol, Josep M. [0000-0001-8621-0057], Fernández-Irigoyen, Joaquín [0000-0001-5072-4099], Fernandez-Puente, Patricia [0000-0001-9968-1034], Froment, Carine [0000-0003-3688-5560], Fuentes-Almagro, Carlos [0000-0001-9940-9065], Gay, Marina [0000-0002-8827-7092], Heller, Manfred [0000-0002-6364-7325], Ibarrola, Nieves [0000-0002-9259-5739], Iloro, Ibon [0000-0002-9537-1714], Kieselbach, Thomas [0000-0001-5577-2938], Lario, Antonio [0000-0002-7457-2402], Locard-Paulet, Marie [0000-0003-2879-9224], Morato-López, Esperanza [0000-0003-4768-895X], Muñoz, Javier [0000-0003-3288-3496], Navajas, Rosana [0000-0002-4481-0553], Odena, Maria Antonia [0000-0002-4530-7829], Oliveira, Eliandre [0000-0003-4771-5719], Paradela, Alberto [0000-0001-6837-7056], Ríos, Vivian de los [0000-0001-5582-6879], Ruiz-Romero, Cristina [0000-0001-7649-9803], Sabidó, Eduard 0000-0001-6506-7714], Sánchez del Pino, Manuel M. [0000-0001-9696-7600], Sancho, Jaime [0000-0003-3852-7951], Santamaría, Enrique [0000-0001-8046-8102], Schaeffer-Reiss, Christine [0000-0003-0672-1979], Valero, M. Luz [0000-0002-2082-4600], Vilaseca, Marta [0000-0002-1666-1300], Canals, Francesc [0000-0002-0650-1135], Colomé, Nuria, Abián, Joaquín, Aloria, Kerman, Arizmendi, Jesús M., Barceló-Batllori, Silvia, Braga-Lagache, Sophie, Burlet-Schiltz, Odile, Carrascal, Montserrat, Casal, J. Ignacio, Chicano-Gálvez, Eduardo, Chiva, Cristina, Clemente, Luis Felipe, Elortza, Felix, Estanyol, Josep M., Fernández-Irigoyen, Joaquín, Fernandez-Puente, Patricia, Fidalgo, María José, Froment, Carine, Fuentes, Manuel, Fuentes-Almagro, Carlos, Gay, Marina, Hainard, Alexandre, Heller, Manfred, Hernández, María Luisa, Ibarrola, Nieves, Iloro, Ibon, Kieselbach, Thomas, Lario, Antonio, Locard-Paulet, Marie, Marina, Anabel, Martín, Luna, Morato-López, Esperanza, Muñoz, Javier, Navajas, Rosana, Odena, Maria Antonia, Odriozola, Leticia, Oliveira, Eliandre, Paradela, Alberto, Pasquarello, Carla, Ríos, Vivian de los, Ruiz-Romero, Cristina, Sabidó, Eduard, Sánchez del Pino, Manuel M., Sancho, Jaime, Santamaría, Enrique, Schaeffer-Reiss, Christine, Schneider, Justine, De la Torre, Carolina, Valero, M. Luz, Vilaseca, Marta, Wu, Shuai, Wu, Linfeng, Ximénez de Embún, Pilar, Canals, Francesc, Corrales, Fernando J., ProteoRed-ISCIII, EuPA, Instituto de Salud Carlos III, Abián, Joaquín [0000-0003-2823-5429], Aloria, Kerman [0000-0001-7268-7700], Arizmendi, Jesús M. [0000-0002-1412-4042], Barceló-Batllori, Silvia [0000-0002-5352-9747], Burlet-Schiltz, Odile [0000-0002-3606-2356], Carrascal, Montserrat [0000-0002-0205-2176], Casal, J. Ignacio [0000-0003-1085-2840], Chicano-Gálvez, Eduardo [0000-0002-9481-9628], Chiva, Cristina [0000-0001-8150-6203], Elortza, Felix [0000-0001-8839-5438], Estanyol, Josep M. [0000-0001-8621-0057], Fernández-Irigoyen, Joaquín [0000-0001-5072-4099], Fernandez-Puente, Patricia [0000-0001-9968-1034], Froment, Carine [0000-0003-3688-5560], Fuentes-Almagro, Carlos [0000-0001-9940-9065], Gay, Marina [0000-0002-8827-7092], Heller, Manfred [0000-0002-6364-7325], Ibarrola, Nieves [0000-0002-9259-5739], Iloro, Ibon [0000-0002-9537-1714], Kieselbach, Thomas [0000-0001-5577-2938], Lario, Antonio [0000-0002-7457-2402], Locard-Paulet, Marie [0000-0003-2879-9224], Morato-López, Esperanza [0000-0003-4768-895X], Muñoz, Javier [0000-0003-3288-3496], Navajas, Rosana [0000-0002-4481-0553], Odena, Maria Antonia [0000-0002-4530-7829], Oliveira, Eliandre [0000-0003-4771-5719], Paradela, Alberto [0000-0001-6837-7056], Ríos, Vivian de los [0000-0001-5582-6879], Ruiz-Romero, Cristina [0000-0001-7649-9803], Sabidó, Eduard 0000-0001-6506-7714], Sánchez del Pino, Manuel M. [0000-0001-9696-7600], Sancho, Jaime [0000-0003-3852-7951], Santamaría, Enrique [0000-0001-8046-8102], Schaeffer-Reiss, Christine [0000-0003-0672-1979], Valero, M. Luz [0000-0002-2082-4600], Vilaseca, Marta [0000-0002-1666-1300], Canals, Francesc [0000-0002-0650-1135], Colomé, Nuria, Abián, Joaquín, Aloria, Kerman, Arizmendi, Jesús M., Barceló-Batllori, Silvia, Braga-Lagache, Sophie, Burlet-Schiltz, Odile, Carrascal, Montserrat, Casal, J. Ignacio, Chicano-Gálvez, Eduardo, Chiva, Cristina, Clemente, Luis Felipe, Elortza, Felix, Estanyol, Josep M., Fernández-Irigoyen, Joaquín, Fernandez-Puente, Patricia, Fidalgo, María José, Froment, Carine, Fuentes, Manuel, Fuentes-Almagro, Carlos, Gay, Marina, Hainard, Alexandre, Heller, Manfred, Hernández, María Luisa, Ibarrola, Nieves, Iloro, Ibon, Kieselbach, Thomas, Lario, Antonio, Locard-Paulet, Marie, Marina, Anabel, Martín, Luna, Morato-López, Esperanza, Muñoz, Javier, Navajas, Rosana, Odena, Maria Antonia, Odriozola, Leticia, Oliveira, Eliandre, Paradela, Alberto, Pasquarello, Carla, Ríos, Vivian de los, Ruiz-Romero, Cristina, Sabidó, Eduard, Sánchez del Pino, Manuel M., Sancho, Jaime, Santamaría, Enrique, Schaeffer-Reiss, Christine, Schneider, Justine, De la Torre, Carolina, Valero, M. Luz, Vilaseca, Marta, Wu, Shuai, Wu, Linfeng, Ximénez de Embún, Pilar, Canals, Francesc, Corrales, Fernando J., ProteoRed-ISCIII, and EuPA

Abstract

Global analysis of protein phosphorylation by mass spectrometry proteomic techniques has emerged in the last decades as a powerful tool in biological and biomedical research. However, there are several factors that make the global study of the phosphoproteome more challenging than measuring non-modified proteins. The low stoichiometry of the phosphorylated species and the need to retrieve residue specific information require particular attention on sample preparation, data acquisition and processing to ensure reproducibility, qualitative and quantitative robustness and ample phosphoproteome coverage in phosphoproteomic workflows. Aiming to investigate the effect of different variables in the performance of proteome wide phosphoprotein analysis protocols, ProteoRed-ISCIII and EuPA launched the Proteomics Multicentric Experiment 11 (PME11). A reference sample consisting of a yeast protein extract spiked in with different amounts of a phosphomix standard (Sigma/Merck) was distributed to 31 laboratories around the globe. Thirty-six datasets from 23 laboratories were analyzed. Our results indicate the suitability of the PME11 reference sample to benchmark and optimize phosphoproteomics strategies, weighing the influence of different factors, as well as to rank intra and inter laboratory performance.

Published
2022

19. Supplementary Figure Legend from Snail1-Dependent Activation of Cancer-Associated Fibroblast Controls Epithelial Tumor Cell Invasion and Metastasis

Author

Alba-Castellón, Lorena, primary, Olivera-Salguero, Rubén, primary, Mestre-Farrera, Aida, primary, Peña, Raúl, primary, Herrera, Mercedes, primary, Bonilla, Félix, primary, Casal, J. Ignacio, primary, Baulida, Josep, primary, Peña, Cristina, primary, and García de Herreros, Antonio, primary

Published
2023
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20. Supplementary Methods from Proteome Profiling of Cancer-Associated Fibroblasts Identifies Novel Proinflammatory Signatures and Prognostic Markers for Colorectal Cancer

Author

Torres, Sofia, primary, Bartolomé, Rubén A., primary, Mendes, Marta, primary, Barderas, Rodrigo, primary, Fernandez-Aceñero, M. Jesús, primary, Peláez-García, Alberto, primary, Peña, Cristina, primary, Lopez-Lucendo, María, primary, Villar-Vázquez, Roi, primary, de Herreros, Antonio García, primary, Bonilla, Felix, primary, and Casal, J. Ignacio, primary

Published
2023
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22. Supplementary Table S3 from LOXL2 Is Highly Expressed in Cancer-Associated Fibroblasts and Associates to Poor Colon Cancer Survival

Author

Torres, Sofía, primary, Garcia-Palmero, Irene, primary, Herrera, Mercedes, primary, Bartolomé, Rubén A., primary, Peña, Cristina, primary, Fernandez-Aceñero, M. Jesús, primary, Padilla, Guillermo, primary, Peláez-García, Alberto, primary, Lopez-Lucendo, María, primary, Rodriguez-Merlo, Rufo, primary, de Herreros, Antonio García, primary, Bonilla, Félix, primary, and Casal, J. Ignacio, primary

Published
2023
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23. Supplementary Methods from LOXL2 Is Highly Expressed in Cancer-Associated Fibroblasts and Associates to Poor Colon Cancer Survival

Author

Torres, Sofía, primary, Garcia-Palmero, Irene, primary, Herrera, Mercedes, primary, Bartolomé, Rubén A., primary, Peña, Cristina, primary, Fernandez-Aceñero, M. Jesús, primary, Padilla, Guillermo, primary, Peláez-García, Alberto, primary, Lopez-Lucendo, María, primary, Rodriguez-Merlo, Rufo, primary, de Herreros, Antonio García, primary, Bonilla, Félix, primary, and Casal, J. Ignacio, primary

Published
2023
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25. Supplementary Figures 1 - 5 from Proteome Profiling of Cancer-Associated Fibroblasts Identifies Novel Proinflammatory Signatures and Prognostic Markers for Colorectal Cancer

Author

Torres, Sofia, primary, Bartolomé, Rubén A., primary, Mendes, Marta, primary, Barderas, Rodrigo, primary, Fernandez-Aceñero, M. Jesús, primary, Peláez-García, Alberto, primary, Peña, Cristina, primary, Lopez-Lucendo, María, primary, Villar-Vázquez, Roi, primary, de Herreros, Antonio García, primary, Bonilla, Felix, primary, and Casal, J. Ignacio, primary

Published
2023
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27. Supplementary Table 1 from Proteome Profiling of Cancer-Associated Fibroblasts Identifies Novel Proinflammatory Signatures and Prognostic Markers for Colorectal Cancer

Author

Torres, Sofia, primary, Bartolomé, Rubén A., primary, Mendes, Marta, primary, Barderas, Rodrigo, primary, Fernandez-Aceñero, M. Jesús, primary, Peláez-García, Alberto, primary, Peña, Cristina, primary, Lopez-Lucendo, María, primary, Villar-Vázquez, Roi, primary, de Herreros, Antonio García, primary, Bonilla, Felix, primary, and Casal, J. Ignacio, primary

Published
2023
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28. Supplementary Table 4 from Proteome Profiling of Cancer-Associated Fibroblasts Identifies Novel Proinflammatory Signatures and Prognostic Markers for Colorectal Cancer

Author

Torres, Sofia, primary, Bartolomé, Rubén A., primary, Mendes, Marta, primary, Barderas, Rodrigo, primary, Fernandez-Aceñero, M. Jesús, primary, Peláez-García, Alberto, primary, Peña, Cristina, primary, Lopez-Lucendo, María, primary, Villar-Vázquez, Roi, primary, de Herreros, Antonio García, primary, Bonilla, Felix, primary, and Casal, J. Ignacio, primary

Published
2023
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29. Supplementary figures S1-7 from LOXL2 Is Highly Expressed in Cancer-Associated Fibroblasts and Associates to Poor Colon Cancer Survival

Author

Torres, Sofía, primary, Garcia-Palmero, Irene, primary, Herrera, Mercedes, primary, Bartolomé, Rubén A., primary, Peña, Cristina, primary, Fernandez-Aceñero, M. Jesús, primary, Padilla, Guillermo, primary, Peláez-García, Alberto, primary, Lopez-Lucendo, María, primary, Rodriguez-Merlo, Rufo, primary, de Herreros, Antonio García, primary, Bonilla, Félix, primary, and Casal, J. Ignacio, primary

Published
2023
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30. Supplementary Table 2 from Proteome Profiling of Cancer-Associated Fibroblasts Identifies Novel Proinflammatory Signatures and Prognostic Markers for Colorectal Cancer

Author

Torres, Sofia, primary, Bartolomé, Rubén A., primary, Mendes, Marta, primary, Barderas, Rodrigo, primary, Fernandez-Aceñero, M. Jesús, primary, Peláez-García, Alberto, primary, Peña, Cristina, primary, Lopez-Lucendo, María, primary, Villar-Vázquez, Roi, primary, de Herreros, Antonio García, primary, Bonilla, Felix, primary, and Casal, J. Ignacio, primary

Published
2023
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31. Supplementary Table 3 from Proteome Profiling of Cancer-Associated Fibroblasts Identifies Novel Proinflammatory Signatures and Prognostic Markers for Colorectal Cancer

Author

Torres, Sofia, primary, Bartolomé, Rubén A., primary, Mendes, Marta, primary, Barderas, Rodrigo, primary, Fernandez-Aceñero, M. Jesús, primary, Peláez-García, Alberto, primary, Peña, Cristina, primary, Lopez-Lucendo, María, primary, Villar-Vázquez, Roi, primary, de Herreros, Antonio García, primary, Bonilla, Felix, primary, and Casal, J. Ignacio, primary

Published
2023
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32. Supplementary Methods and References from Snail1-Dependent Activation of Cancer-Associated Fibroblast Controls Epithelial Tumor Cell Invasion and Metastasis

Author

Alba-Castellón, Lorena, primary, Olivera-Salguero, Rubén, primary, Mestre-Farrera, Aida, primary, Peña, Raúl, primary, Herrera, Mercedes, primary, Bonilla, Félix, primary, Casal, J. Ignacio, primary, Baulida, Josep, primary, Peña, Cristina, primary, and García de Herreros, Antonio, primary

Published
2023
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33. Supplementary Table 5 from Proteome Profiling of Cancer-Associated Fibroblasts Identifies Novel Proinflammatory Signatures and Prognostic Markers for Colorectal Cancer

Author

Torres, Sofia, primary, Bartolomé, Rubén A., primary, Mendes, Marta, primary, Barderas, Rodrigo, primary, Fernandez-Aceñero, M. Jesús, primary, Peláez-García, Alberto, primary, Peña, Cristina, primary, Lopez-Lucendo, María, primary, Villar-Vázquez, Roi, primary, de Herreros, Antonio García, primary, Bonilla, Felix, primary, and Casal, J. Ignacio, primary

Published
2023
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34. Supplementary Table 6 - 10 from Proteome Profiling of Cancer-Associated Fibroblasts Identifies Novel Proinflammatory Signatures and Prognostic Markers for Colorectal Cancer

Author

Torres, Sofia, primary, Bartolomé, Rubén A., primary, Mendes, Marta, primary, Barderas, Rodrigo, primary, Fernandez-Aceñero, M. Jesús, primary, Peláez-García, Alberto, primary, Peña, Cristina, primary, Lopez-Lucendo, María, primary, Villar-Vázquez, Roi, primary, de Herreros, Antonio García, primary, Bonilla, Felix, primary, and Casal, J. Ignacio, primary

Published
2023
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35. Supplementary Figures S1-S14 from Snail1-Dependent Activation of Cancer-Associated Fibroblast Controls Epithelial Tumor Cell Invasion and Metastasis

Author

Alba-Castellón, Lorena, primary, Olivera-Salguero, Rubén, primary, Mestre-Farrera, Aida, primary, Peña, Raúl, primary, Herrera, Mercedes, primary, Bonilla, Félix, primary, Casal, J. Ignacio, primary, Baulida, Josep, primary, Peña, Cristina, primary, and García de Herreros, Antonio, primary

Published
2023
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42. Functional Proteomics Characterization of the Role of SPRYD7 in Colorectal Cancer Progression and Metastasis

Author

Instituto de Salud Carlos III, European Commission, Ministerio de Educación, Cultura y Deporte (España), Montero-Calle, Ana, Jiménez de Ocaña, Sofía, Benavente-Naranjo, Ruth, Rejas-González, Raquel, Bartolomé, Rubén Álvaro, Martínez-Useros, Javier, Sanz, Rodrigo, Dziaková, Jana, Fernandez-Aceñero, M. Jesús, Mendiola, Marta, Casal, J. Ignacio, Peláez-García, Alberto, Barderas, Rodrigo, Instituto de Salud Carlos III, European Commission, Ministerio de Educación, Cultura y Deporte (España), Montero-Calle, Ana, Jiménez de Ocaña, Sofía, Benavente-Naranjo, Ruth, Rejas-González, Raquel, Bartolomé, Rubén Álvaro, Martínez-Useros, Javier, Sanz, Rodrigo, Dziaková, Jana, Fernandez-Aceñero, M. Jesús, Mendiola, Marta, Casal, J. Ignacio, Peláez-García, Alberto, and Barderas, Rodrigo

Abstract

SPRY domain-containing protein 7 (SPRYD7) is a barely known protein identified via spatial proteomics as being upregulated in highly metastatic-to-liver KM12SM colorectal cancer (CRC) cells in comparison to its isogenic poorly metastatic KM12C CRC cells. Here, we aimed to analyze SPRYD7’s role in CRC via functional proteomics. Through immunohistochemistry, the overexpression of SPRYD7 was observed to be associated with the poor survival of CRC patients and with an aggressive and metastatic phenotype. Stable SPRYD7 overexpression was performed in KM12C and SW480 poorly metastatic CRC cells and in their isogenic highly metastatic-to-liver-KM12SM-and-to-lymph-nodes SW620 CRC cells, respectively. Upon upregulation of SPRYD7, in vitro and in vivo functional assays confirmed a key role of SPRYD7 in the invasion and migration of CRC cells and in liver homing and tumor growth. Additionally, transient siRNA SPRYD7 silencing allowed us to confirm in vitro functional results. Furthermore, SPRYD7 was observed as an inductor of angiogenesis. In addition, the dysregulated SPRYD7-associated proteome and SPRYD7 interactors were elucidated via 10-plex TMT quantitative proteins, immunoproteomics, and bioinformatics. After WB validation, the biological pathways associated with the stable overexpression of SPRYD7 were visualized. In conclusion, it was demonstrated here that SPRYD7 is a novel protein associated with CRC progression and metastasis. Thus, SPRYD7 and its interactors might be of relevance in identifying novel therapeutic targets for advanced CRC.

Published
2023

43. Agentes que se unen específicamente al motivo RGD de la cadherina 17 humana, la cadherina 5 humana, la cadherina 6 humana y la cadherina 20 humana

Author

Casal, J. Ignacio, Bartolomé, Rubén Álvaro, Casal, J. Ignacio, and Bartolomé, Rubén Álvaro

Abstract

La descripción se refiere a agentes que se unen específicamente a la cadherina 17 humana (CDH17) y/o a la cadherina 5 humana (CDH5) y/o a la cadherina 6 humana (CDH6) y/o a la cadherina 20 humana (CDH20). La divulgación también se relaciona con el uso de estos agentes en terapia, métodos para diagnóstico y/o pronóstico y/o estratificación de un cáncer en un sujeto, y composiciones farmacéuticas que comprenden dichos agentes. La divulgación también se refiere a marcadores de cáncer y marcadores de metástasis.

Published
2023

46. Looking for novel interactors of IL-13 receptor α2 (IL13Rα2) and tyrosine-protein phosphatase non-receptor type 1 (PTPN1/PTP1B) by using proximity-dependent biotinylation (BioID)

Author

Martin-Regalado, Ángela, Bartolomé, Rubén Álvaro, Robles, Javier, Jaén, Marta, Pintado-Berninches, Laura, Boukich, Issam, Ríos, Vivian de los, Casal, J. Ignacio, Martin-Regalado, Ángela, Bartolomé, Rubén Álvaro, Robles, Javier, Jaén, Marta, Pintado-Berninches, Laura, Boukich, Issam, Ríos, Vivian de los, and Casal, J. Ignacio

Abstract

2 p., Introduction IL13Rα2 is a high affinity receptor for IL-13 that is re-expressed in late neoplastic stages. The IL-13/IL13Rα2 axis triggers invasion in colorectal cancer (CRC) and other cancers in a process mediated, among others, by the phosphatase PTPN1 (aka PTP1B), involved in the dephosphorylation of the autoinhibitory Src Tyr416 and further Src activation. PTPN1 takes part in IL13Rα2 internalization and associates with poor outcome in glioblastoma and CRC patients. Inhibition of IL13Rα2 pathway decreases invasion of multiple cancer cell lines (i.e., SKOV-3, PC-3 and KM12SM). To better define the oncogenic properties of IL13Rα2 and PTPN1, we aim to identify novel interactors by using proximity-dependent biotinylation coupled to mass spectrometry., Material and Methods PTPN1 and IL13Rα2 were cloned into pcDNA.5-pDEST-BirA-Flag-Ct by using LR clonase enzyme, obtaining the desired plasmids containing fusion genes PTPN1-BirA and IL13Rα2-BirA. Flp-In™ T-REx™ cells were co-transfected with pOG44 and pcDNA.5 vectors and selected with hygromycin. Then doxycycline and biotin were added to induce the expression of the fusion gene and proximity labelling. Biotinylated proteins were purified by affinity using streptavidin-sepharose, trypsin-digested and analysed in a Q-Exactive mass spectrometer. Raw data were analysed with MaxQuant, followed by Perseus for statistical analysis and SAINT for probabilistic scoring of protein-protein interaction data, which were subjected to gene ontology (GO) analysis., Results and Discussions For IL13Rα2, 735 proteins were identified and 94 were scored as significant interactors by SAINT. GO enrichment analysis showed association with cadherin binding and response to reticulum stress, among others. 1009 proteins were identified and 217 were scored as significant PTPN1 interactors. GO enrichment analysis showed important association with mitotic cell cycle regulation, such as CDK1 (G2/M transition) or PCTN (centrosome component). Among the 19 IL13Rα2 and PTPN1 common interactors stand out those related to SNARE complex (YKT6, SNAP29 and VAMP3), which is involved in regulation of cancer invasion, drug resistance and kinase phosphorylation. Another interesting finding was the presence of VRK2, a kinase involved in MAPK pathway, Conclusion This study reveals novel individual interactors of IL13Rα2 and PTPN1, but also identifies common interactors of both proteins such as members of the SNARE complex and VRK2, opening new strategies for the inhibition of IL13Rα2 and PTPN1 in cancer metastasis.

Published
2022

47. CDH17 as a biomarker and target of chemoresistance to irinotecan

Author

Jaén, Marta, Bartolomé, Rubén Álvaro, Pintado-Berninches, Laura, Martin-Regalado, Ángela, Robles, Javier, Boukich, Issam, Aizpurua, Carmen, Ríos, Vivian de los, Imbaud, Juan Ignacio, Casal, J. Ignacio, Jaén, Marta, Bartolomé, Rubén Álvaro, Pintado-Berninches, Laura, Martin-Regalado, Ángela, Robles, Javier, Boukich, Issam, Aizpurua, Carmen, Ríos, Vivian de los, Imbaud, Juan Ignacio, and Casal, J. Ignacio

Abstract

2 p., Introduction Cadherin 17 (CDH17) plays a key role in colorectal cancer (CRC) metastasis. CDH17 binds and activates α2β1 integrin, through its RGD motif, promoting cell adhesion and proliferation. Blocking this interaction using RGD-specific monoclonal antibodies (mAbs) inhibited the metastatic capacity in mouse models. In a previous report, an overexpression of CDH17 in CRC cells treated with irinotecan was observed. Here, our goal was to investigate the participation of CDH17 in chemotherapy resistance mechanisms and to test the efficacy of RGD CDH17 mAbs in irinotecan-resistant cells., Material and Methods We generated irinotecan-resistant CRC cell lines (COLO205,KM12SM,SW620) by increasing the irinotecan dose from 0.05 to 0.5 mM. Cells were analyzed by Western Blot (WB), flow cytometry (FC) and qPCR assays to study expression of CDH17 and other proteins involved in chemoresistance (i.e. MDR1, ABCG2) or epithelial–mesenchymal transition mediators. In addition, cell cycle and the adhesive and proliferative properties of resistant cells were analyzed in the presence or absence of RGD-specific mAbs to test its efficacy. Then, CDH17 was silenced to determine its role in irinotecan chemoresistance. Finally, we performed a label-free proteomic quantification to survey global changes in proteins of wt cells compared to resistant cells., Results and Discussions CRC cell lines resistant to 0.5 μM irinotecan increased their epithelial phenotype with an overexpression of CDH17, ITGA2, CDX2, MDR1, ABCG2 and ALDH1A markers as determined by WB and FC. In agreement with these results, an increase in adhesion was observed in irinotecan-treated cells. Cell cycle in resistant cells showed preferential arrest in G2/M phase, as irinotecan inhibits the action of topoisomerase I. Proteins involved in chemoresistance, tumorigenesis or modulation of tumor response were founded dysregulated after proteomic analysis of resistant cells. Interestingly, resistant cells were more sensitive to the inhibitory effects of RGD-specific mAb. However, CDH17-silencing experiments in resistant and parental cells indicated that CDH17 was not involved in the mechanisms of resistance to irinotecan., Conclusion CDH17 has shown to be a specific marker of irinotecan-resistance and, therefore, a good target for CDH17 RGD-specific mAb. Therefore, patients that develop resistance to irinotecan could benefit from this therapy.

Published
2022

48. A Proteomic Analysis Reveals That Snail Regulates the Expression of the Nuclear Orphan Receptor Nuclear Receptor Subfamily 2 Group F Member 6 (Nr2f6) and Interleukin 17 (IL-17) to Inhibit Adipocyte Differentiation *

Author

Peláez-García, Alberto, Barderas, Rodrigo, Batlle, Raquel, Viñas-Castells, Rosa, Bartolomé, Rubén A., Torres, Sofía, Mendes, Marta, Lopez-Lucendo, María, Mazzolini, Rocco, Bonilla, Félix, de Herreros, Antonio García, and Casal, J. Ignacio

Published
2015
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50. Proteomic analysis of low-grade, early-stage endometrialcarcinoma reveals new dysregulated pathways associated with cell death and cell signaling

Author

Instituto de Salud Carlos III, European Commission, López-Janeiro, Álvaro [0000-0002-5744-3115], Ruz-Caracuel, Ignacio [0000-0002-2298-4683], Ramón-Patino, Jorge L. [0000-0002-7308-823X], Ríos, Vivian de los [0000-0001-5582-6879], Villalba Esparza, María [0000-0002-9183-0610], Berjón, Alberto [0000-0002-3467-106X], Kadioglu, Ece [0000-0001-8679-8030], Heredia-Soto, Victoria [0000-0002-0704-7958], Barderas, Rodrigo [0000-0003-3539-7469], Casal, J. Ignacio [0000-0003-1085-2840], De Andrea, Carlos E. [0000-0002-7628-8050], Mendiola, Marta [0000-0002-2463-1304], Peláez-García, Alberto [0000-0002-5401-3216], Hardisson, David [0000-0002-2183-3699], López-Janeiro, Álvaro, Ruz-Caracuel, Ignacio, Ramón-Patino, Jorge L., Ríos, Vivian de los, Villalba Esparza, María, Berjón, Alberto, Yébenes, Laura, Hernández, Alicia, Masetto, Ivan, Kadioglu, Ece, Goubert, Virginie, Heredia-Soto, Victoria, Barderas, Rodrigo, Casal, J. Ignacio, De Andrea, Carlos E., Redondo, Andrés, Mendiola, Marta, Peláez-García, Alberto, Hardisson, David, Instituto de Salud Carlos III, European Commission, López-Janeiro, Álvaro [0000-0002-5744-3115], Ruz-Caracuel, Ignacio [0000-0002-2298-4683], Ramón-Patino, Jorge L. [0000-0002-7308-823X], Ríos, Vivian de los [0000-0001-5582-6879], Villalba Esparza, María [0000-0002-9183-0610], Berjón, Alberto [0000-0002-3467-106X], Kadioglu, Ece [0000-0001-8679-8030], Heredia-Soto, Victoria [0000-0002-0704-7958], Barderas, Rodrigo [0000-0003-3539-7469], Casal, J. Ignacio [0000-0003-1085-2840], De Andrea, Carlos E. [0000-0002-7628-8050], Mendiola, Marta [0000-0002-2463-1304], Peláez-García, Alberto [0000-0002-5401-3216], Hardisson, David [0000-0002-2183-3699], López-Janeiro, Álvaro, Ruz-Caracuel, Ignacio, Ramón-Patino, Jorge L., Ríos, Vivian de los, Villalba Esparza, María, Berjón, Alberto, Yébenes, Laura, Hernández, Alicia, Masetto, Ivan, Kadioglu, Ece, Goubert, Virginie, Heredia-Soto, Victoria, Barderas, Rodrigo, Casal, J. Ignacio, De Andrea, Carlos E., Redondo, Andrés, Mendiola, Marta, Peláez-García, Alberto, and Hardisson, David

Abstract

Low-grade, early-stage endometrial carcinoma (EC) is the most frequent malignant tumor of the uterine corpus. However, the molecular alterations that underlie these tumors are far from being fully understood. The purpose of this study is to describe dysregulated molecular pathways from EC patients. Sixteen samples of tumor tissue and paired healthy controls were collected and both were subjected to mass spectrometry (MS)/MS proteomic analysis. Gene ontology and pathway analysis was performed to discover dysregulated pathways and/or proteins using different databases and bioinformatic tools. Dysregulated pathways were cross-validated in an independent external cohort. Cell signaling, immune response, and cell death-associated pathways were robustly identified. The SLIT/ROBO signaling pathway demonstrated dysregulation at the proteomic and transcriptomic level. Necroptosis and ferroptosis were cell death-associated processes aberrantly regulated, in addition to apoptosis. Immune response-associated pathways showed a dominance of innate immune responses. Tumor immune infiltrates measured by immunofluorescence demonstrated diverse lymphoid and myeloid populations. Our results suggest a role of SLIT/ROBO, necroptosis, and ferroptosis, as well as a prominent role of innate immune response in low-grade, early-stage EC. These results could guide future research in this group of tumors

Published
2021

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