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3. Tumors defective in homologous recombination rely on oxidative metabolism: relevance to treatments with PARP inhibitors

Author

Lahiguera, Álvaro, Hyroššová, Petra, Figueras, Agnès, Garzón, Diana, Moreno, Roger, Soto‐Cerrato, Vanessa, McNeish, Iain, Serra, Violeta, Lazaro, Conxi, Barretina, Pilar, Brunet, Joan, Menéndez, Javier, Matias‐Guiu, Xavier, Vidal, August, Villanueva, Alberto, Taylor‐Harding, Barbie, Tanaka, Hisashi, Orsulic, Sandra, Junza, Alexandra, Yanes, Oscar, Muñoz‐Pinedo, Cristina, Palomero, Luís, Pujana, Miquel Àngel, Perales, José Carlos, and Viñals, Francesc

Subjects
Cancer, Genetics, Biotechnology, Aetiology, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, 2.1 Biological and endogenous factors, Carcinoma, Ovarian Epithelial, Female, Homologous Recombination, Humans, Ovarian Neoplasms, Oxidative Stress, Poly(ADP-ribose) Polymerase Inhibitors, BCRA, cancer metabolism, metformin, OXPHOS, PARP inhibitors, BCRA, OXPHOS, Biological Sciences, Medical and Health Sciences
Abstract

Mitochondrial metabolism and the generation of reactive oxygen species (ROS) contribute to the acquisition of DNA mutations and genomic instability in cancer. How genomic instability influences the metabolic capacity of cancer cells is nevertheless poorly understood. Here, we show that homologous recombination-defective (HRD) cancers rely on oxidative metabolism to supply NAD+ and ATP for poly(ADP-ribose) polymerase (PARP)-dependent DNA repair mechanisms. Studies in breast and ovarian cancer HRD models depict a metabolic shift that includes enhanced expression of the oxidative phosphorylation (OXPHOS) pathway and its key components and a decline in the glycolytic Warburg phenotype. Hence, HRD cells are more sensitive to metformin and NAD+ concentration changes. On the other hand, shifting from an OXPHOS to a highly glycolytic metabolism interferes with the sensitivity to PARP inhibitors (PARPi) in these HRD cells. This feature is associated with a weak response to PARP inhibition in patient-derived xenografts, emerging as a new mechanism to determine PARPi sensitivity. This study shows a mechanistic link between two major cancer hallmarks, which in turn suggests novel possibilities for specifically treating HRD cancers with OXPHOS inhibitors.

Published
2020

7. Histamine signaling and metabolism identify potential biomarkers and therapies for lymphangioleiomyomatosis

Author

Herranz, Carmen, Mateo, Francesca, Baiges, Alexandra, Ruiz de Garibay, Gorka, Junza, Alexandra, Johnson, Simon R, Miller, Suzanne, García, Nadia, Capellades, Jordi, Gómez, Antonio, Vidal, August, Palomero, Luis, Espín, Roderic, Extremera, Ana I, Blommaert, Eline, Revilla‐López, Eva, Saez, Berta, Gómez‐Ollés, Susana, Ancochea, Julio, Valenzuela, Claudia, Alonso, Tamara, Ussetti, Piedad, Laporta, Rosalía, Xaubet, Antoni, Rodríguez‐Portal, José A, Montes‐Worboys, Ana, Machahua, Carlos, Bordas, Jaume, Menendez, Javier A, Cruzado, Josep M, Guiteras, Roser, Bontoux, Christophe, La Motta, Concettina, Noguera‐Castells, Aleix, Mancino, Mario, Lastra, Enrique, Rigo‐Bonnin, Raúl, Perales, Jose C, Viñals, Francesc, Lahiguera, Alvaro, Zhang, Xiaohu, Cuadras, Daniel, van Moorsel, Coline H M, van der Vis, Joanne J, Quanjel, Marian J R, Filippakis, Harilaos, Hakem, Razq, Gorrini, Chiara, Ferrer, Marc, Ugun‐Klusek, Aslihan, Billett, Ellen, Radzikowska, Elżbieta, Casanova, Álvaro, Molina‐Molina, María, Roman, Antonio, Yanes, Oscar, and Pujana, Miquel A

Published
2021
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8. Ovarian cancer relies on the PDGFRβ–fibronectin axis for tumorsphere formation and metastatic spread

Author

Gendrau‐Sanclemente, Núria, primary, Figueras, Agnès, additional, Gracova, Kristina, additional, Lahiguera, Álvaro, additional, Alsina‐Sanchís, Elisenda, additional, Marín‐Jiménez, Juan A., additional, Vidal, August, additional, Matias‐Guiu, Xavier, additional, Fernandez‐Gonzalez, Sergi, additional, Barahona, Marc, additional, Martí, Lola, additional, Ponce, Jordi, additional, and Viñals, Francesc, additional

Published
2023
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10. Ovarian cancer relies on the PDGFRβ–fibronectin axis for tumorsphere formation and metastatic spread.

Author

Gendrau‐Sanclemente, Núria, Figueras, Agnès, Gracova, Kristina, Lahiguera, Álvaro, Alsina‐Sanchís, Elisenda, Marín‐Jiménez, Juan A., Vidal, August, Matias‐Guiu, Xavier, Fernandez‐Gonzalez, Sergi, Barahona, Marc, Martí, Lola, Ponce, Jordi, and Viñals, Francesc

Abstract

High‐grade serous ovarian cancer (HGSOC) is the deadliest gynecological malignancy. The most common form of metastatic spread of HGSOC is transcoelomic dissemination. In this process, detached cells from the primary tumor aggregate as tumorspheres and promote the accumulation of peritoneal ascites. This represents an early event in HGSOC development and is indicative of poor prognosis. In this study, based on tumorspheres isolated from ascitic liquid samples from HGSOC patients, ovarian cancer spheroid 3D cultures, and in vivo models, we describe a key signal for tumorsphere formation in HGSOC. We report that platelet‐derived growth factor receptor beta (PDGFRβ) is essential for fibronectin‐mediated cell clustering of ovarian cancer cells into tumorspheres. This effect is mediated by the kinase NUAK family SNF1‐like kinase 1 (NUAK1) and blocked by PDGFRβ pharmacological or genetic inhibition. In the absence of PDGFRβ, ovarian cancer cells can be provided with fibronectin by cancer‐associated fibroblasts to generate chimeric spheroids. This work provides new insights that uncover potential targets to prevent peritoneal dissemination, the main cause of advanced disease in HGSOC patients. [ABSTRACT FROM AUTHOR]

Published
2024
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12. Supplementary Figures 1-12 from A Role for CXCR4 in Peritoneal and Hematogenous Ovarian Cancer Dissemination

Author

Figueras, Agnès, primary, Alsina-Sanchís, Elisenda, primary, Lahiguera, Álvaro, primary, Abreu, Manuel, primary, Muinelo-Romay, Laura, primary, Moreno-Bueno, Gema, primary, Casanovas, Oriol, primary, Graupera, Mariona, primary, Matias-Guiu, Xavier, primary, Vidal, August, primary, Villanueva, Alberto, primary, and Viñals, Francesc, primary

Published
2023
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18. Data from Sunitinib Inhibits Tumor Growth and Synergizes with Cisplatin in Orthotopic Models of Cisplatin-Sensitive and Cisplatin-Resistant Human Testicular Germ Cell Tumors

Author

Castillo-Ávila, Wilmar, primary, Piulats, Josep Maria, primary, Garcia del Muro, Xavier, primary, Vidal, August, primary, Condom, Enric, primary, Casanovas, Oriol, primary, Mora, Josefina, primary, Germà, Josep Ramon, primary, Capellà, Gabriel, primary, Villanueva, Alberto, primary, and Viñals, Francesc, primary

Published
2023
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20. Supplementary fig 2 from Orthoxenografts of Testicular Germ Cell Tumors Demonstrate Genomic Changes Associated with Cisplatin Resistance and Identify PDMP as a Resensitizing Agent

Author

Piulats, Josep M., primary, Vidal, August, primary, García-Rodríguez, Francisco J., primary, Muñoz, Clara, primary, Nadal, Marga, primary, Moutinho, Catia, primary, Martínez-Iniesta, María, primary, Mora, Josefina, primary, Figueras, Agnés, primary, Guinó, Elisabet, primary, Padullés, Laura, primary, Aytés, Àlvaro, primary, Molleví, David G., primary, Puertas, Sara, primary, Martínez-Fernández, Carmen, primary, Castillo, Wilmar, primary, Juliachs, Merce, primary, Moreno, Victor, primary, Muñoz, Purificación, primary, Stefanovic, Milica, primary, Pujana, Miguel A., primary, Condom, Enric, primary, Esteller, Manel, primary, Germà, Josep R., primary, Capella, Gabriel, primary, Farré, Lourdes, primary, Morales, Albert, primary, Viñals, Francesc, primary, García-del-Muro, Xavier, primary, Cerón, Julián, primary, and Villanueva, Alberto, primary

Published
2023
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21. Supplementary Data from FGFR Inhibition Overcomes Resistance to EGFR-targeted Therapy in Epithelial-like Cutaneous Carcinoma

Author

Bernat-Peguera, Adrià, primary, Navarro-Ventura, Juan, primary, Lorenzo-Sanz, Laura, primary, da Silva-Diz, Victoria, primary, Bosio, Mattia, primary, Palomero, Luis, primary, Penin, Rosa M., primary, Pérez Sidelnikova, Diana, primary, Bermejo, Josep Oriol, primary, Taberna, Miren, primary, Vilariño, Noelia, primary, Piulats, Josep M., primary, Mesia, Ricard, primary, Viñals, Joan Maria, primary, González-Suárez, Eva, primary, Capella-Gutierrez, Salvador, primary, Villanueva, Alberto, primary, Viñals, Francesc, primary, and Muñoz, Purificación, primary

Published
2023
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22. Suplementary fig 3 from Orthoxenografts of Testicular Germ Cell Tumors Demonstrate Genomic Changes Associated with Cisplatin Resistance and Identify PDMP as a Resensitizing Agent

Author

Piulats, Josep M., primary, Vidal, August, primary, García-Rodríguez, Francisco J., primary, Muñoz, Clara, primary, Nadal, Marga, primary, Moutinho, Catia, primary, Martínez-Iniesta, María, primary, Mora, Josefina, primary, Figueras, Agnés, primary, Guinó, Elisabet, primary, Padullés, Laura, primary, Aytés, Àlvaro, primary, Molleví, David G., primary, Puertas, Sara, primary, Martínez-Fernández, Carmen, primary, Castillo, Wilmar, primary, Juliachs, Merce, primary, Moreno, Victor, primary, Muñoz, Purificación, primary, Stefanovic, Milica, primary, Pujana, Miguel A., primary, Condom, Enric, primary, Esteller, Manel, primary, Germà, Josep R., primary, Capella, Gabriel, primary, Farré, Lourdes, primary, Morales, Albert, primary, Viñals, Francesc, primary, García-del-Muro, Xavier, primary, Cerón, Julián, primary, and Villanueva, Alberto, primary

Published
2023
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23. Supplementary fig 5 from Orthoxenografts of Testicular Germ Cell Tumors Demonstrate Genomic Changes Associated with Cisplatin Resistance and Identify PDMP as a Resensitizing Agent

Author

Piulats, Josep M., primary, Vidal, August, primary, García-Rodríguez, Francisco J., primary, Muñoz, Clara, primary, Nadal, Marga, primary, Moutinho, Catia, primary, Martínez-Iniesta, María, primary, Mora, Josefina, primary, Figueras, Agnés, primary, Guinó, Elisabet, primary, Padullés, Laura, primary, Aytés, Àlvaro, primary, Molleví, David G., primary, Puertas, Sara, primary, Martínez-Fernández, Carmen, primary, Castillo, Wilmar, primary, Juliachs, Merce, primary, Moreno, Victor, primary, Muñoz, Purificación, primary, Stefanovic, Milica, primary, Pujana, Miguel A., primary, Condom, Enric, primary, Esteller, Manel, primary, Germà, Josep R., primary, Capella, Gabriel, primary, Farré, Lourdes, primary, Morales, Albert, primary, Viñals, Francesc, primary, García-del-Muro, Xavier, primary, Cerón, Julián, primary, and Villanueva, Alberto, primary

Published
2023
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24. Supplementary Figure 1 from Lurbinectedin (PM01183), a New DNA Minor Groove Binder, Inhibits Growth of Orthotopic Primary Graft of Cisplatin-Resistant Epithelial Ovarian Cancer

Author

Vidal, August, primary, Muñoz, Clara, primary, Guillén, María-José, primary, Moretó, Jemina, primary, Puertas, Sara, primary, Martínez-Iniesta, María, primary, Figueras, Agnés, primary, Padullés, Laura, primary, García-Rodriguez, Francisco J., primary, Berdiel-Acer, Mireia, primary, Pujana, Miguel A., primary, Salazar, Ramón, primary, Gil-Martin, Marta, primary, Martí, Lola, primary, Ponce, Jordi, primary, Molleví, David G., primary, Capella, Gabriel, primary, Condom, Enric, primary, Viñals, Francesc, primary, Huertas, Dori, primary, Cuevas, Carmen, primary, Esteller, Manel, primary, Avilés, Pablo, primary, and Villanueva, Alberto, primary

Published
2023
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25. Supplementary Table 1 from Lurbinectedin (PM01183), a New DNA Minor Groove Binder, Inhibits Growth of Orthotopic Primary Graft of Cisplatin-Resistant Epithelial Ovarian Cancer

Author

Vidal, August, primary, Muñoz, Clara, primary, Guillén, María-José, primary, Moretó, Jemina, primary, Puertas, Sara, primary, Martínez-Iniesta, María, primary, Figueras, Agnés, primary, Padullés, Laura, primary, García-Rodriguez, Francisco J., primary, Berdiel-Acer, Mireia, primary, Pujana, Miguel A., primary, Salazar, Ramón, primary, Gil-Martin, Marta, primary, Martí, Lola, primary, Ponce, Jordi, primary, Molleví, David G., primary, Capella, Gabriel, primary, Condom, Enric, primary, Viñals, Francesc, primary, Huertas, Dori, primary, Cuevas, Carmen, primary, Esteller, Manel, primary, Avilés, Pablo, primary, and Villanueva, Alberto, primary

Published
2023
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26. Supplementary Data from Sunitinib Inhibits Tumor Growth and Synergizes with Cisplatin in Orthotopic Models of Cisplatin-Sensitive and Cisplatin-Resistant Human Testicular Germ Cell Tumors

Author

Castillo-Ávila, Wilmar, primary, Piulats, Josep Maria, primary, Garcia del Muro, Xavier, primary, Vidal, August, primary, Condom, Enric, primary, Casanovas, Oriol, primary, Mora, Josefina, primary, Germà, Josep Ramon, primary, Capellà, Gabriel, primary, Villanueva, Alberto, primary, and Viñals, Francesc, primary

Published
2023
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27. Supplementary figure 1 from Orthoxenografts of Testicular Germ Cell Tumors Demonstrate Genomic Changes Associated with Cisplatin Resistance and Identify PDMP as a Resensitizing Agent

Author

Piulats, Josep M., primary, Vidal, August, primary, García-Rodríguez, Francisco J., primary, Muñoz, Clara, primary, Nadal, Marga, primary, Moutinho, Catia, primary, Martínez-Iniesta, María, primary, Mora, Josefina, primary, Figueras, Agnés, primary, Guinó, Elisabet, primary, Padullés, Laura, primary, Aytés, Àlvaro, primary, Molleví, David G., primary, Puertas, Sara, primary, Martínez-Fernández, Carmen, primary, Castillo, Wilmar, primary, Juliachs, Merce, primary, Moreno, Victor, primary, Muñoz, Purificación, primary, Stefanovic, Milica, primary, Pujana, Miguel A., primary, Condom, Enric, primary, Esteller, Manel, primary, Germà, Josep R., primary, Capella, Gabriel, primary, Farré, Lourdes, primary, Morales, Albert, primary, Viñals, Francesc, primary, García-del-Muro, Xavier, primary, Cerón, Julián, primary, and Villanueva, Alberto, primary

Published
2023
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29. Supplementary data from Orthoxenografts of Testicular Germ Cell Tumors Demonstrate Genomic Changes Associated with Cisplatin Resistance and Identify PDMP as a Resensitizing Agent

Author

Piulats, Josep M., primary, Vidal, August, primary, García-Rodríguez, Francisco J., primary, Muñoz, Clara, primary, Nadal, Marga, primary, Moutinho, Catia, primary, Martínez-Iniesta, María, primary, Mora, Josefina, primary, Figueras, Agnés, primary, Guinó, Elisabet, primary, Padullés, Laura, primary, Aytés, Àlvaro, primary, Molleví, David G., primary, Puertas, Sara, primary, Martínez-Fernández, Carmen, primary, Castillo, Wilmar, primary, Juliachs, Merce, primary, Moreno, Victor, primary, Muñoz, Purificación, primary, Stefanovic, Milica, primary, Pujana, Miguel A., primary, Condom, Enric, primary, Esteller, Manel, primary, Germà, Josep R., primary, Capella, Gabriel, primary, Farré, Lourdes, primary, Morales, Albert, primary, Viñals, Francesc, primary, García-del-Muro, Xavier, primary, Cerón, Julián, primary, and Villanueva, Alberto, primary

Published
2023
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30. Supplementary fig 4 from Orthoxenografts of Testicular Germ Cell Tumors Demonstrate Genomic Changes Associated with Cisplatin Resistance and Identify PDMP as a Resensitizing Agent

Author

Piulats, Josep M., primary, Vidal, August, primary, García-Rodríguez, Francisco J., primary, Muñoz, Clara, primary, Nadal, Marga, primary, Moutinho, Catia, primary, Martínez-Iniesta, María, primary, Mora, Josefina, primary, Figueras, Agnés, primary, Guinó, Elisabet, primary, Padullés, Laura, primary, Aytés, Àlvaro, primary, Molleví, David G., primary, Puertas, Sara, primary, Martínez-Fernández, Carmen, primary, Castillo, Wilmar, primary, Juliachs, Merce, primary, Moreno, Victor, primary, Muñoz, Purificación, primary, Stefanovic, Milica, primary, Pujana, Miguel A., primary, Condom, Enric, primary, Esteller, Manel, primary, Germà, Josep R., primary, Capella, Gabriel, primary, Farré, Lourdes, primary, Morales, Albert, primary, Viñals, Francesc, primary, García-del-Muro, Xavier, primary, Cerón, Julián, primary, and Villanueva, Alberto, primary

Published
2023
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31. Supplementary Figure 1 from RANK Induces Epithelial–Mesenchymal Transition and Stemness in Human Mammary Epithelial Cells and Promotes Tumorigenesis and Metastasis

Author

Palafox, Marta, primary, Ferrer, Irene, primary, Pellegrini, Pasquale, primary, Vila, Sergi, primary, Hernandez-Ortega, Sara, primary, Urruticoechea, Ander, primary, Climent, Fina, primary, Soler, Maria Teresa, primary, Muñoz, Purificación, primary, Viñals, Francesc, primary, Tometsko, Mark, primary, Branstetter, Dan, primary, Dougall, William C., primary, and González-Suárez, Eva, primary

Published
2023
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32. Supplementary Figures 1 through 7, Supplementary Tables 1 and 3, and Supplementary Materials and Methods from Cancer Stem-like Cells Act via Distinct Signaling Pathways in Promoting Late Stages of Malignant Progression

Author

da Silva-Diz, Victoria, primary, Simón-Extremera, Pilar, primary, Bernat-Peguera, Adrià, primary, de Sostoa, Jana, primary, Urpí, Maria, primary, Penín, Rosa M., primary, Sidelnikova, Diana Pérez, primary, Bermejo, Oriol, primary, Viñals, Joan Maria, primary, Rodolosse, Annie, primary, González-Suárez, Eva, primary, Moruno, Antonio Gómez, primary, Pujana, Miguel Ángel, primary, Esteller, Manel, primary, Villanueva, Alberto, primary, Viñals, Francesc, primary, and Muñoz, Purificación, primary

Published
2023
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33. Supplementary Figure 7 from RANK Induces Epithelial–Mesenchymal Transition and Stemness in Human Mammary Epithelial Cells and Promotes Tumorigenesis and Metastasis

Author

Palafox, Marta, primary, Ferrer, Irene, primary, Pellegrini, Pasquale, primary, Vila, Sergi, primary, Hernandez-Ortega, Sara, primary, Urruticoechea, Ander, primary, Climent, Fina, primary, Soler, Maria Teresa, primary, Muñoz, Purificación, primary, Viñals, Francesc, primary, Tometsko, Mark, primary, Branstetter, Dan, primary, Dougall, William C., primary, and González-Suárez, Eva, primary

Published
2023
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34. Supplementary Figure 5 from RANK Induces Epithelial–Mesenchymal Transition and Stemness in Human Mammary Epithelial Cells and Promotes Tumorigenesis and Metastasis

Author

Palafox, Marta, primary, Ferrer, Irene, primary, Pellegrini, Pasquale, primary, Vila, Sergi, primary, Hernandez-Ortega, Sara, primary, Urruticoechea, Ander, primary, Climent, Fina, primary, Soler, Maria Teresa, primary, Muñoz, Purificación, primary, Viñals, Francesc, primary, Tometsko, Mark, primary, Branstetter, Dan, primary, Dougall, William C., primary, and González-Suárez, Eva, primary

Published
2023
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35. Supplementary Table 2 from Cancer Stem-like Cells Act via Distinct Signaling Pathways in Promoting Late Stages of Malignant Progression

Author

da Silva-Diz, Victoria, primary, Simón-Extremera, Pilar, primary, Bernat-Peguera, Adrià, primary, de Sostoa, Jana, primary, Urpí, Maria, primary, Penín, Rosa M., primary, Sidelnikova, Diana Pérez, primary, Bermejo, Oriol, primary, Viñals, Joan Maria, primary, Rodolosse, Annie, primary, González-Suárez, Eva, primary, Moruno, Antonio Gómez, primary, Pujana, Miguel Ángel, primary, Esteller, Manel, primary, Villanueva, Alberto, primary, Viñals, Francesc, primary, and Muñoz, Purificación, primary

Published
2023
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36. Supplementary Methods, Figure Legends 1-7 from RANK Induces Epithelial–Mesenchymal Transition and Stemness in Human Mammary Epithelial Cells and Promotes Tumorigenesis and Metastasis

Author

Palafox, Marta, primary, Ferrer, Irene, primary, Pellegrini, Pasquale, primary, Vila, Sergi, primary, Hernandez-Ortega, Sara, primary, Urruticoechea, Ander, primary, Climent, Fina, primary, Soler, Maria Teresa, primary, Muñoz, Purificación, primary, Viñals, Francesc, primary, Tometsko, Mark, primary, Branstetter, Dan, primary, Dougall, William C., primary, and González-Suárez, Eva, primary

Published
2023
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37. Data from RANK Induces Epithelial–Mesenchymal Transition and Stemness in Human Mammary Epithelial Cells and Promotes Tumorigenesis and Metastasis

Author

Palafox, Marta, primary, Ferrer, Irene, primary, Pellegrini, Pasquale, primary, Vila, Sergi, primary, Hernandez-Ortega, Sara, primary, Urruticoechea, Ander, primary, Climent, Fina, primary, Soler, Maria Teresa, primary, Muñoz, Purificación, primary, Viñals, Francesc, primary, Tometsko, Mark, primary, Branstetter, Dan, primary, Dougall, William C., primary, and González-Suárez, Eva, primary

Published
2023
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38. Supplementary Figure 3 from RANK Induces Epithelial–Mesenchymal Transition and Stemness in Human Mammary Epithelial Cells and Promotes Tumorigenesis and Metastasis

Author

Palafox, Marta, primary, Ferrer, Irene, primary, Pellegrini, Pasquale, primary, Vila, Sergi, primary, Hernandez-Ortega, Sara, primary, Urruticoechea, Ander, primary, Climent, Fina, primary, Soler, Maria Teresa, primary, Muñoz, Purificación, primary, Viñals, Francesc, primary, Tometsko, Mark, primary, Branstetter, Dan, primary, Dougall, William C., primary, and González-Suárez, Eva, primary

Published
2023
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39. Supplementary Figure 4 from RANK Induces Epithelial–Mesenchymal Transition and Stemness in Human Mammary Epithelial Cells and Promotes Tumorigenesis and Metastasis

Author

Palafox, Marta, primary, Ferrer, Irene, primary, Pellegrini, Pasquale, primary, Vila, Sergi, primary, Hernandez-Ortega, Sara, primary, Urruticoechea, Ander, primary, Climent, Fina, primary, Soler, Maria Teresa, primary, Muñoz, Purificación, primary, Viñals, Francesc, primary, Tometsko, Mark, primary, Branstetter, Dan, primary, Dougall, William C., primary, and González-Suárez, Eva, primary

Published
2023
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40. Supplementary Figure 2 from RANK Induces Epithelial–Mesenchymal Transition and Stemness in Human Mammary Epithelial Cells and Promotes Tumorigenesis and Metastasis

Author

Palafox, Marta, primary, Ferrer, Irene, primary, Pellegrini, Pasquale, primary, Vila, Sergi, primary, Hernandez-Ortega, Sara, primary, Urruticoechea, Ander, primary, Climent, Fina, primary, Soler, Maria Teresa, primary, Muñoz, Purificación, primary, Viñals, Francesc, primary, Tometsko, Mark, primary, Branstetter, Dan, primary, Dougall, William C., primary, and González-Suárez, Eva, primary

Published
2023
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41. Supplementary Figure 6 from RANK Induces Epithelial–Mesenchymal Transition and Stemness in Human Mammary Epithelial Cells and Promotes Tumorigenesis and Metastasis

Author

Palafox, Marta, primary, Ferrer, Irene, primary, Pellegrini, Pasquale, primary, Vila, Sergi, primary, Hernandez-Ortega, Sara, primary, Urruticoechea, Ander, primary, Climent, Fina, primary, Soler, Maria Teresa, primary, Muñoz, Purificación, primary, Viñals, Francesc, primary, Tometsko, Mark, primary, Branstetter, Dan, primary, Dougall, William C., primary, and González-Suárez, Eva, primary

Published
2023
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43. Generation and Integrated Analysis of Advanced Patient‐Derived Orthoxenograft Models (PDOX) for the Rational Assessment of Targeted Therapies in Endometrial Cancer

Author

Devis‐Jauregui, Laura, primary, Vidal, August, additional, Plata‐Peña, Laura, additional, Santacana, Maria, additional, García‐Mulero, Sandra, additional, Bonifaci, Nuria, additional, Noguera‐Delgado, Eulàlia, additional, Ruiz, Nuria, additional, Gil, Marta, additional, Dorca, Eduard, additional, Llobet, Francisco J., additional, Coll‐Iglesias, Laura, additional, Gassner, Katja, additional, Martinez‐Iniesta, Maria, additional, Rodriguez‐Barrueco, Ruth, additional, Barahona, Marc, additional, Marti, Lola, additional, Viñals, Francesc, additional, Ponce, Jordi, additional, Sanz‐Pamplona, Rebeca, additional, Piulats, Josep M., additional, Vivancos, Ana, additional, Matias‐Guiu, Xavier, additional, Villanueva, Alberto, additional, and Llobet‐Navas, David, additional

Published
2022
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45. Endothelial cell rearrangements during vascular patterning require PI3-kinase-mediated inhibition of actomyosin contractility

Author

Angulo-Urarte, Ana, Casado, Pedro, Castillo, Sandra D., Kobialka, Piotr, Kotini, Maria Paraskevi, Figueiredo, Ana M., Castel, Pau, Rajeeve, Vinothini, Milà-Guasch, Maria, Millan, Jaime, Wiesner, Cora, Serra, Helena, Muixi, Laia, Casanovas, Oriol, Viñals, Francesc, Affolter, Markus, Gerhardt, Holger, Huveneers, Stephan, Belting, Heinz-Georg, Cutillas, Pedro R., and Graupera, Mariona

Published
2018
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46. S

Author

Vinals, Francesc, Pouysségur, Jacques, Rappaport, Lydie, Chassagne, Catherine, Samuel, Jane-Lyse, and Bikfalvi, Andreas

Published
2000
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47. Glycosylation defects, offset by PEPCK-M, drive entosis in breast carcinoma cells

Author

Ministerio de Ciencia e Innovación (España), Generalitat de Catalunya, European Commission, Ministerio de Educación (España), Universidad de Barcelona, Hyroššová, P., Aragó, Marc, Muñoz-Pinedo, Cristina, Viñals, Francesc, García-Rovés, Pablo M., Escolano, Carmen, Méndez-Lucas, A., Perales, José C., Ministerio de Ciencia e Innovación (España), Generalitat de Catalunya, European Commission, Ministerio de Educación (España), Universidad de Barcelona, Hyroššová, P., Aragó, Marc, Muñoz-Pinedo, Cristina, Viñals, Francesc, García-Rovés, Pablo M., Escolano, Carmen, Méndez-Lucas, A., and Perales, José C.

Abstract

On glucose restriction, epithelial cells can undergo entosis, a cell-in-cell cannibalistic process, to allow considerable withstanding to this metabolic stress. Thus, we hypothesized that reduced protein glycosylation might participate in the activation of this cell survival pathway. Glucose deprivation promoted entosis in an MCF7 breast carcinoma model, as evaluated by direct inspection under the microscope, or revealed by a shift to apoptosis + necrosis in cells undergoing entosis treated with a Rho-GTPase kinase inhibitor (ROCKi). In this context, curbing protein glycosylation defects with N-acetyl-glucosamine partially rescued entosis, whereas limiting glycosylation in the presence of glucose with tunicamycin or NGI-1, but not with other unrelated ER-stress inducers such as thapsigargin or amino-acid limitation, stimulated entosis. Mitochondrial phosphoenolpyruvate carboxykinase (PEPCK-M; PCK2) is upregulated by glucose deprivation, thereby enhancing cell survival. Therefore, we presumed that PEPCK-M could play a role in this process by offsetting key metabolites into glycosyl moieties using alternative substrates. PEPCK-M inhibition using iPEPCK-2 promoted entosis in the absence of glucose, whereas its overexpression inhibited entosis. PEPCK-M inhibition had a direct role on total protein glycosylation as determined by Concanavalin A binding, and the specific ratio of fully glycosylated LAMP1 or E-cadherin. The content of metabolites, and the fluxes from C-glutamine label into glycolytic intermediates up to glucose-6-phosphate, and ribose- and ribulose-5-phosphate, was dependent on PEPCK-M content as measured by GC/MS. All in all, we demonstrate for the first time that protein glycosylation defects precede and initiate the entosis process and implicates PEPCK-M in this survival program to dampen the consequences of glucose deprivation. These results have broad implications to our understanding of tumor metabolism and treatment strategies.

Published
2022

50. Correction: Corrigendum: A DERL3-associated defect in the degradation of SLC2A1 mediates the Warburg effect

Author

Lopez-Serra, Paula, Marcilla, Miguel, Villanueva, Alberto, Ramos-Fernandez, Antonio, Palau, Anna, Leal, Lucía, Wahi, Jessica E., Setien-Baranda, Fernando, Szczesna, Karolina, Moutinho, Catia, Martinez-Cardus, Anna, Heyn, Holger, Sandoval, Juan, Puertas, Sara, Vidal, August, Sanjuan, Xavier, Martinez-Balibrea, Eva, Viñals, Francesc, Perales, Jose C., Bramsem, Jesper B., Ørntoft, Torben F., Andersen, Claus L., Tabernero, Josep, McDermott, Ultan, Boxer, Matthew B., Vander Heiden, Matthew G., Albar, Juan Pablo, and Esteller, Manel

Published
2016
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