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4. Exercise and tumor proteome: insights from a neuroblastoma model.

Author

Plaza-Florido, Abel, Gálvez, Beatriz G., López, Juan A., Santos-Lozano, Alejandro, Zazo, Sandra, Rincón-Castanedo, Cecilia, Martín-Ruiz, Asunción, Lumbreras, Jorge, Terron-Camero, Laura C., López-Soto, Alejandro, Andrés-León, Eduardo, González-Murillo, África, Rojo, Federico, Ramírez, Manuel, Lucia, Alejandro, and Fiuza-Luces, Carmen

Subjects
LIQUID chromatography-mass spectrometry, EXERCISE physiology, PEROXISOME proliferator-activated receptors, AMINO acid metabolism, FALSE discovery rate, RESISTANCE training
Abstract

The impact of exercise on pediatric tumor biology is essentially unknown. We explored the effects of regular exercise on tumor proteome profile (as assessed with liquid chromatography with tandem mass spectrometry) in a mouse model of one of the most aggressive childhood malignancies, high-risk neuroblastoma (HR-NB). Tumor samples of 14 male mice (aged 6–8 wk) that were randomly allocated into an exercise (5-wk combined aerobic and resistance training) or nonexercise control group (6 and 8 mice/group, respectively) were analyzed. The Search Tool for the Retrieval of Interacting Genes/Proteins database was used to generate a protein-protein interaction (PPI) network and enrichment analyses. The Systems Biology Triangle (SBT) algorithm was applied for analyses at the functional category level. Tumors of exercised mice showed a higher and lower abundance of 101 and 150 proteins, respectively, than controls [false discovery rate (FDR) < 0.05]. These proteins were enriched in metabolic pathways, amino acid metabolism, regulation of hormone levels, and peroxisome proliferator-activated receptor signaling (FDR < 0.05). The SBT algorithm indicated that 184 and 126 categories showed a lower and higher abundance, respectively, in the tumors of exercised mice (FDR < 0.01). Categories with lower abundance were involved in energy production, whereas those with higher abundance were related to transcription/translation, apoptosis, and tumor suppression. Regular exercise altered the abundance of hundreds of intratumoral proteins and molecular pathways, particularly those involved in energy metabolism, apoptosis, and tumor suppression. These findings provide preliminary evidence of the molecular mechanisms underlying the potential effects of exercise in HR-NB. NEW & NOTEWORTHY: We used liquid chromatography with tandem mass spectrometry to explore the impact of a 5-wk exercise intervention on the tumor proteome profile in a mouse model of one of the most aggressive childhood malignancies, high-risk neuroblastoma. Exercise altered the abundance of hundreds of proteins and pathways, particularly those involved in energy metabolism and tumor suppression. These molecular changes could mediate, at least partly, the potential antitumorigenic effects of exercise. [ABSTRACT FROM AUTHOR]

Published
2024
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5. Autophagy‐linked plasma and lysosomal membrane protein PLAC8 is a key host factor for SARS‐CoV‐2 entry into human cells

Author

Ugalde, Alejandro P, Bretones, Gabriel, Rodríguez, David, Quesada, Víctor, Llorente, Francisco, Fernández‐Delgado, Raúl, Jiménez‐Clavero, Miguel Ángel, Vázquez, Jesús, Calvo, Enrique, Tamargo‐Gómez, Isaac, Mariño, Guillermo, Roiz‐Valle, David, Maeso, Daniel, Araujo‐Voces, Miguel, Español, Yaiza, Barceló, Carles, Freije, José MP, López‐Soto, Alejandro, and López‐Otín, Carlos

Published
2022
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7. Daratumumab is a safe and effective rescue therapy for multiple myeloma patients who relapse after allo-HSCT

Author

Gonzalez-Rodriguez, Ana Pilar, Lopez-Corral, Lucia, Fajardo, David Fernando Moreno, Gonzalez-Huerta, Ana Julia, Palomo, Pilar, Bermudez, Arantxa, Ripa, Teresa Zudaire, Santos-Diaz, Patricia, Gonzalez-Muñiz, Soledad, Zanabilli, Joud, Jimenez Ubieto, Ana, de Arriba, Felipe, Arnao-Herraiz, Mario, Sordo-Bahamonde, Christian, López-Soto, Alejandro, Gonzalez, Segundo, Rosiñol, Laura, and Mateos, María-Victoria

Published
2020
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10. The secretome atlas of two mouse models of progeria

Author

Quintana‐Torres, Diego, primary, Valle‐Cao, Alejandra, additional, Bousquets‐Muñoz, Pablo, additional, Freitas‐Rodríguez, Sandra, additional, Rodríguez, Francisco, additional, Lucia, Alejandro, additional, López‐Otín, Carlos, additional, López‐Soto, Alejandro, additional, and Folgueras, Alicia R., additional

Published
2023
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22. Table S3 from NK-cell Editing Mediates Epithelial-to-Mesenchymal Transition via Phenotypic and Proteomic Changes in Melanoma Cell Lines

Author

Huergo-Zapico, Leticía, primary, Parodi, Monica, primary, Cantoni, Claudia, primary, Lavarello, Chiara, primary, Fernández-Martínez, Juan L., primary, Petretto, Andrea, primary, DeAndrés-Galiana, Enrique J., primary, Balsamo, Mirna, primary, López-Soto, Alejandro, primary, Pietra, Gabriella, primary, Bugatti, Mattia, primary, Munari, Enrico, primary, Marconi, Marcella, primary, Mingari, Maria Cristina, primary, Vermi, William, primary, Moretta, Lorenzo, primary, González, Segundo, primary, and Vitale, Massimo, primary

Published
2023
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23. SI Materials and Methods from NK-cell Editing Mediates Epithelial-to-Mesenchymal Transition via Phenotypic and Proteomic Changes in Melanoma Cell Lines

Author

Huergo-Zapico, Leticía, primary, Parodi, Monica, primary, Cantoni, Claudia, primary, Lavarello, Chiara, primary, Fernández-Martínez, Juan L., primary, Petretto, Andrea, primary, DeAndrés-Galiana, Enrique J., primary, Balsamo, Mirna, primary, López-Soto, Alejandro, primary, Pietra, Gabriella, primary, Bugatti, Mattia, primary, Munari, Enrico, primary, Marconi, Marcella, primary, Mingari, Maria Cristina, primary, Vermi, William, primary, Moretta, Lorenzo, primary, González, Segundo, primary, and Vitale, Massimo, primary

Published
2023
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24. Figures S1-S13 from NK-cell Editing Mediates Epithelial-to-Mesenchymal Transition via Phenotypic and Proteomic Changes in Melanoma Cell Lines

Author

Huergo-Zapico, Leticía, primary, Parodi, Monica, primary, Cantoni, Claudia, primary, Lavarello, Chiara, primary, Fernández-Martínez, Juan L., primary, Petretto, Andrea, primary, DeAndrés-Galiana, Enrique J., primary, Balsamo, Mirna, primary, López-Soto, Alejandro, primary, Pietra, Gabriella, primary, Bugatti, Mattia, primary, Munari, Enrico, primary, Marconi, Marcella, primary, Mingari, Maria Cristina, primary, Vermi, William, primary, Moretta, Lorenzo, primary, González, Segundo, primary, and Vitale, Massimo, primary

Published
2023
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25. Autophagy-linked plasma and lysosomal membrane protein PLAC8 is a key host factor for SARS-CoV-2 entry into human cells

Author

Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Fundación la Caixa, Principado de Asturias, Ugalde, Alejandro P., Bretones, Gabriel, Rodríguez, David, Quesada, Víctor, Llorente, Francisco, Fernandez-Delgado, Raúl, Jiménez-Clavero, Miguel Ángel, Vázquez, Jesús, Calvo, Enrique, Tamargo-Gómez, Isaac, Mariño, Guillermo, Roiz-Valle, David, Maeso, Daniel, Araujo-Voces, Miguel, Español, Yaiza, Barceló, Carlos, Freije, José M. P., López-Soto, Alejandro, López-Otín, Carlos, Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Fundación la Caixa, Principado de Asturias, Ugalde, Alejandro P., Bretones, Gabriel, Rodríguez, David, Quesada, Víctor, Llorente, Francisco, Fernandez-Delgado, Raúl, Jiménez-Clavero, Miguel Ángel, Vázquez, Jesús, Calvo, Enrique, Tamargo-Gómez, Isaac, Mariño, Guillermo, Roiz-Valle, David, Maeso, Daniel, Araujo-Voces, Miguel, Español, Yaiza, Barceló, Carlos, Freije, José M. P., López-Soto, Alejandro, and López-Otín, Carlos

Abstract

Better understanding on interactions between SARS-CoV-2andhost cells should help to identify host factors that may be tar-getable to combat infection and COVID-19pathology. To this end,we have conducted a genome-wide CRISPR/Cas9-based loss-of-function screen in human lung cancer cells infected with SARS-CoV-2-pseudotyped lentiviruses. Our results recapitulate manyfindings from previous screens that used full SARS-CoV-2viruses,but also unveil two novel critical host factors: the lysosomal effluxtransporter SPNS1and the plasma and lysosomal membrane pro-tein PLAC8. Functional experiments with full SARS-CoV-2virusesconfirm that loss-of-function of these genes impairs viral entry.We find that PLAC8is a key limiting host factor, whose overexpres-sion boosts viral infection in eight different human lung cancer celllines. Using single-cell RNA-Seq data analyses, we demonstratethat PLAC8is highly expressed in ciliated and secretory cells of therespiratory tract, as well as in gut enterocytes, cell types that arehighly susceptible to SARS-CoV-2infection. Proteomics and cellbiology studies suggest that PLAC8and SPNS1regulate theautophagolysosomal compartment and affect the intracellular fateof endocytosed virions.

Published
2022

26. Contributors

Author

Amadori, Massimo, primary, Fukui, Ryutaro, additional, Gallucci, Stefania, additional, González, Segundo, additional, Lacetera, Nicola, additional, López-Larrea, Carlos, additional, López-Soto, Alejandro, additional, Mantere, Outi, additional, Maru, Yoshiro, additional, Miyake, Kensuke, additional, Moscati, Livia, additional, Razzuoli, Elisabetta, additional, Riboldi, Elena, additional, Sica, Antonio, additional, Suvisaari, Jaana, additional, Trevisi, Erminio, additional, and Zanotti, Cinzia, additional

Published
2016
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32. Exercise training effects on natural killer cells: a preliminary proteomics and systems biology approach

Author

Llavero Bernal, Francisco, Brea Alejo, Lidia, Fiuza Luces, María del Carmen, López Soto, Alejandro, Valenzuela Tallón, Pedro Luis, Castillo García, Adrián, Morales Rojas, Javier Salvador, Fernández, David, Pagola Aldazabal, Itziar, and Lucía Mulas, Alejandro

Subjects
Citotoxicidad inmunológica, Biología celular, Inmunología, Deporte, Entrenamiento aeróbico
Abstract

Background: Regular exercise, particularly moderate-intensity continuous training (MICT), can improve immune function. Natural killer (NK) cells, a subset of lymphocytes that react to infections, are the most responsive innate immune cells to exercise, but the mechanisms underlying this are poorly understood. A type of exercise training that is gaining popularity in recent years is high-intensity interval training (HIIT), but how it affects NK cells is largely unknown. In fact, intense exercise has been traditionally viewed as a potential stressor to immune homeostasis. The purpose of this study was to determine in healthy, previously untrained adults (N=8 [3 male; 40±6 years]) the effects of an intervention consisting of 4-week MICT followed by 4-week HIIT on NK cells as compared with a pre-training (baseline) state. Methods: Participants were studied at three time points: baseline, mid-intervention (after MICT), and post-intervention (after HIIT). Main assessments included cytotoxicity assays, flow-cytometry analysis of NK cell surface markers, and interrogation of the cellular proteome using a systems biology approach. Results: A significant time effect was found for NK cell cytotoxicity (p 10 and false discovery rate [FDR] q-value < 0.001) were COP9 signalosome subunit 3 (COPS3), DnaJ heat shock protein family member B11 (DNAJB11), histidyl-TRNA synthetase 1 (HARS), NIMA related kinase 9 (NEK9), nucleoporin 88 (NUP88), phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), regulator of chromosome condensation 2 (RCC2), TAO kinase 3 (TAOK3), transducin beta like 2 (TBL2), and ring finger protein 40 (RNF40). All were upregulated at mid-intervention compared with baseline, with the exception of HARS, which was downregulated. Four enriched pathways (FDR p

Published
2021

38. Contributors

Author

Andoniou, Christopher E., primary, Balato, Anna, additional, Basse, Per H., additional, Bekiaris, Vasileios, additional, Bernardini, Giovanni, additional, Briercheck, Edward L., additional, Bryan, Maryanne A., additional, Butterfield, Lisa H., additional, Cahalan, Michael D., additional, Caligiuri, Michael A., additional, Camp, William L., additional, Carlino, Claudia, additional, Carlyle, James R., additional, Carrega, Paolo, additional, Chambers, Benedict J., additional, Chamoto, Kenji, additional, Cooley, Sarah, additional, Costello, Régis, additional, Coudert, Jerome D., additional, Daldrup-Link, Heike, additional, de Armas, Lesley R., additional, Degli-Esposti, Mariapia, additional, Djeu, Julie Y., additional, Epling-Burnette, P.K., additional, Fan, Jia, additional, Fauriat, Cyril, additional, Ferlazzo, Guido, additional, Freud, Aharon G., additional, Garrod, Kym R., additional, Gaspari, Anthony A., additional, Getz, Godfrey S., additional, Gismondi, Angela, additional, Goding, Stephen R., additional, González, Segundo, additional, Goodier, Martin R., additional, Grzywacz, Bartosz, additional, Höglund, Petter, additional, Hosmalin, Anne, additional, Housseau, Franck, additional, Ikeda, Takayuki, additional, Ito, Taisuke, additional, Jha, Priyanka, additional, Kähäri, Veli-Matti, additional, Kanto, Tatsuya, additional, Karlsson-Parra, Alex, additional, Kiessling, Rolf, additional, Klingemann, Hans, additional, Knopp, Christiane, additional, Koizumi, Shinichi, additional, Komoriya, Akira, additional, Kuo, Ming-Ling, additional, Lane, Peter J.L., additional, Lee, Yen-Chang, additional, Liippo, Jussi, additional, Lin, Syh-Jae, additional, Liu, Siyuan, additional, Ljunggren, Hans-Gustaf, additional, López-Larrea, Carlos, additional, López-Soto, Alejandro, additional, Lotze, Michael T., additional, Loux, Tara J., additional, Lu, Lina, additional, Magee, Michael, additional, Mailliard, Robbie B., additional, Male, Victoria H., additional, Mandelboim, Ofer, additional, Masuko, Kazutaka, additional, Matta, Benjamin M., additional, Mavilio, Domenico, additional, Mehrad, Borna, additional, Miller, Jeffery S., additional, Mitamura, Rieko, additional, Moffett, Ashley, additional, Montalto, Erika, additional, Moretta, Alessandro, additional, Moretta, Lorenzo, additional, Morice, William G., additional, Münz, Christian, additional, Nalesnik, Michael A., additional, Niederkorn, Jerry Y., additional, Nishimura, Takashi, additional, Norris, Karen A., additional, Olive, Daniel, additional, Ortaldo, John R., additional, Packard, Beverly Z., additional, Paus, Ralf, additional, Podack, Eckhard R., additional, Qian, Shiguang, additional, Qiu, Shuang-Jian, additional, Ransohoff, Richard M., additional, Reardon, Catherine A., additional, Reinhart, Verena, additional, Rey, Jérôme, additional, Rubartelli, Anna, additional, Santoni, Angela, additional, Scott-Algara, Daniel, additional, Semino, Claudia, additional, Shi, Fu-Dong, additional, Stabile, Helena, additional, Stern-Ginossar, Noam, additional, Subleski, Jeff, additional, Thomson, Angus W., additional, Toriseva, Mervi, additional, Ucker, David S., additional, Velardi, Andrea, additional, Verneris, Michael R., additional, Vujanovic, Lazar N., additional, Vujanovic, Nikola L., additional, Wakita, Daiko, additional, Wei, Sheng, additional, Weiss, Jonathan M., additional, Wels, Winfried S., additional, Wendland, Michael F., additional, Wesa, Amy K., additional, Wiltrout, Robert H., additional, Xiao, Yong-Sheng, additional, Yan, Dah-Chin, additional, Yawata, Makato, additional, Yawata, Nobuyo, additional, Zhang, Alexandra Y., additional, and Zúñiga-Pflücker, Juan Carlos, additional

Published
2010
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44. Daratumumab is a safe and effective rescue therapy for multiple myeloma patients who relapse after allo-HSCT

Author

Instituto de Salud Carlos III, European Commission, Gonzalez-Rodriguez, Ana Pilar, López-Corral, L., Moreno Fajardo, David Fernando, Gonzalez-Huerta, Ana Julia, Palomo, Pilar, Bermúdez, Arantxa, Zudaire Ripa, Teresa, Santos-Diaz, Patricia, Gonzalez-Muñiz, Soledad, Zanabilli, Joud, Jiménez-Ubieto, Ana, Arriba, Felipe de, Arnao‐Herráiz, Mario, Sordo-Bahamonde, Christian, López-Soto, Alejandro, González, Segundo, Rosiñol, Laura, Mateos, Maria Victoria, Instituto de Salud Carlos III, European Commission, Gonzalez-Rodriguez, Ana Pilar, López-Corral, L., Moreno Fajardo, David Fernando, Gonzalez-Huerta, Ana Julia, Palomo, Pilar, Bermúdez, Arantxa, Zudaire Ripa, Teresa, Santos-Diaz, Patricia, Gonzalez-Muñiz, Soledad, Zanabilli, Joud, Jiménez-Ubieto, Ana, Arriba, Felipe de, Arnao‐Herráiz, Mario, Sordo-Bahamonde, Christian, López-Soto, Alejandro, González, Segundo, Rosiñol, Laura, and Mateos, Maria Victoria

Published
2020

45. The Mithralog EC-7072 Induces Chronic Lymphocytic Leukemia Cell Death by Targeting Tonic B-Cell Receptor Signaling

Author

Lorenzo-Herrero, Seila, primary, Sordo-Bahamonde, Christian, additional, Bretones, Gabriel, additional, Payer, Ángel R., additional, González-Rodríguez, Ana P., additional, González-García, Esther, additional, Pérez-Escuredo, Jhudit, additional, Villa-Álvarez, Mónica, additional, Núñez, Luz-Elena, additional, Morís, Francisco, additional, Gonzalez, Segundo, additional, and López-Soto, Alejandro, additional

Published
2019
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47. Daratumumab is a safe and effective rescue therapy for multiple myeloma patients who relapse after allo-HSCT

Author

Gonzalez-Rodriguez, Ana Pilar, primary, Lopez-Corral, Lucia, additional, Fajardo, David Fernando Moreno, additional, Gonzalez-Huerta, Ana Julia, additional, Palomo, Pilar, additional, Bermudez, Arantxa, additional, Ripa, Teresa Zudaire, additional, Santos-Diaz, Patricia, additional, Gonzalez-Muñiz, Soledad, additional, Zanabilli, Joud, additional, Jimenez Ubieto, Ana, additional, de Arriba, Felipe, additional, Arnao-Herraiz, Mario, additional, Sordo-Bahamonde, Christian, additional, López-Soto, Alejandro, additional, Gonzalez, Segundo, additional, Rosiñol, Laura, additional, and Mateos, María-Victoria, additional

Published
2019
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48. Exercise training effects on natural killer cells: a preliminary proteomics and systems biology approach.

Author

Llavero, Francisco, Alejo, Lidia B., Fiuza-Luces, Carmen, López Soto, Alejandro, Valenzuela, Pedro L., Castillo-García, Adrián, Morales, Javier S., Fernández, David, Pagola Aldazabal, Itziar, Ramírez, Manuel, Santos-Lozano, Alejandro, Zugaza, José L., and Lucia, Alejandro

Subjects
KILLER cells, SYSTEMS biology, HIGH-intensity interval training, HEAT shock proteins, FALSE discovery rate
Abstract

Background: Regular exercise, particularly moderate-intensity continuous training (MICT), can improve immune function. Natural killer (NK) cells, a subset of lymphocytes that react to infections, are the most responsive innate immune cells to exercise, but the mechanisms underlying this are poorly understood. A type of exercise training that is gaining popularity in recent years is high-intensity interval training (HIIT), but how it affects NK cells is largely unknown. In fact, intense exercise has been traditionally viewed as a potential stressor to immune homeostasis. The purpose of this study was to determine in healthy, previously untrained adults (N=8 [3 male; 40±6 years]) the effects of an intervention consisting of 4-week MICT followed by 4-week HIIT on NK cells as compared with a pre-training (baseline) state. Methods: Participants were studied at three time points: baseline, mid-intervention (after MICT), and post-intervention (after HIIT). Main assessments included cytotoxicity assays, flow-cytometry analysis of NK cell surface markers, and interrogation of the cellular proteome using a systems biology approach. Results: A significant time effect was found for NK cell cytotoxicity (p<0.001), which was increased ~10-fold at both midand post-intervention versus baseline. No significant intervention effect was found for NK surface receptor expression, except for CXCR3 determined as mean fluorescence intensity (p=0.044, although with no significant differences in post hoc pairwise comparisons). The proteins showing a higher differential expression (Log2 fold-change>10 and false discovery rate [FDR] q-value<0.001) were COP9 signalosome subunit 3 (COPS3), DnaJ heat shock protein family member B11 (DNAJB11), histidyl-TRNA synthetase 1 (HARS), NIMA related kinase 9 (NEK9), nucleoporin 88 (NUP88), phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), regulator of chromosome condensation 2 (RCC2), TAO kinase 3 (TAOK3), transducin beta like 2 (TBL2), and ring finger protein 40 (RNF40). All were upregulated at mid-intervention compared with baseline, with the exception of HARS, which was downregulated. Four enriched pathways (FDR <25%) were found: two related to transmembrane transport and cellular composition (downregulated at mid-intervention vs baseline), and two related to oxidation-reduction reactions (upregulated at post-intervention versus baseline). Conclusions: A progressive exercise intervention of MICT followed by HIIT induces a remarkable improvement in NK function compared with the untrained state, although at the mechanistic level the pathways involved seem to differ over time during the intervention. [ABSTRACT FROM AUTHOR]

Published
2021

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