Person: Lorente Pérez, María Del Mar
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First Name
María Del Mar
Last Name
Lorente Pérez
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Ciencias Químicas
Department
Bioquímica y Biología Molecular
Area
Bioquímica y Biología Molecular
Identifiers
10 results
Search Results
Now showing 1 - 10 of 10
Item POTEE promotes breast cancer cell malignancy by inducing invadopodia formation through the activation of SUMOylated Rac1(2023) Martínez‐López, Angélica; García Casas, Ana; Infante, Guiomar; González‐Fernández, Mónica; Salvador, Nélida; Lorente, Mar; Mendiburu‐Eliçabe, Marina; Gonzalez‐Moreno, Santiago ; Villarejo‐Campos, Pedro ; Malliri, Angeliki ; Lorente Pérez, María Del Mar; Velasco Díez, Guillermo; Castillo Lluva, SoniaTThe small GTPase Rac1 (Ras-related C3 botulinum toxin substrate 1) has been implicated in cancer progression and in the poor prognosis of various types of tumors. Rac1 SUMOylation occurs during epithelial-mesenchymal transition (EMT), and it is required for tumor cell migration and invasion. Here we identify POTEE (POTE Ankyrin domain family member E) as a novel Rac1-SUMO1 effector involved in breast cancer malignancy that controls invadopodium formation through the activation of Rac1-SUMO1. POTEE activates Rac1 in the invadopodium by recruiting TRIO-GEF (triple functional domain protein), and it induces tumor cell proliferation and metastasis in vitro and in vivo. We found that the co-localization of POTEE with Rac1 is correlated with more aggressive breast cancer subtypes. Given its role in tumor dissemination, the leading cause of cancer-related deaths, POTEE could represent a potential therapeutic target for these types of cancer.Item Stromal SNAI2 is required for ERBB2 breast cancer progression(Cancer research, 2020) Blanco Gómez, Adrián; Hontecillas Prieto, Lourdes; Corchado Cobos, Roberto; García Sancha, Natalia; Salvador Tormo, Nélida; Castellanos Martín, Andrés; Sáez Freire, María del Mar; Mendiburu-Eliçabe Garganta, Marina; Alonso López, Diego; De Las Rivas Sanz, Javier; Lorente Pérez, María Del Mar; García Casas, Ana; Del Carmen Martínez, Sofía; Abad Hernández, María del Mar; Cruz Hernández, Juan Jesús; Rodríguez Sánchez, César Augusto; Claros Ampuero, Juncal; García Cenador, Begoña; García Criado, Javier; Orimo, Akira; Gridley, Thomas; Pérez Losada, Jesús; Castillo Lluva, SoniaSNAI2 overexpression appears to be associated with poor prognosis in breast cancer, yet it remains unclear in which breast cancer subtypes this occurs. Here we show that excess SNAI2 is associated with a poor prognosis of luminal B HER2+/ERBB2+ breast cancers in which SNAI2 expression in the stroma but not the epithelium correlates with tumor proliferation. To determine how stromal SNAI2 might influence HER2+ tumor behavior, Snai2-deficient mice were crossed with a mouse line carrying the ErbB2/Neu protooncogene to generate HER2+/ERBB2+ breast cancer. Tumors generated in this model expressed SNAI2 in the stroma but not the epithelium, allowing for the role of stromal SNAI2 to be studied without interference from the epithelial compartment. The absence of SNAI2 in the stroma of HER2+/ERBB2+ tumors is associated with: (i) lower levels of cyclin D1 (CCND1) and reduced tumor epithelium proliferation; (ii) higher levels of AKT and a lower incidence of metastasis; (iii) lower levels of angiopoietin-2 (ANGPT2), and more necrosis. Together, these results indicate that the loss of SNAI2 in cancer-associated fibroblasts limits the production of some cytokines, which influences AKT/ERK tumor signaling and subsequent proliferative and metastatic capacity of ERBB2+ breast cancer cells. Accordingly, SNAI2 expression in the stroma enhanced the tumorigenicity of luminal B HER2+/ERBB2+ breast cancers. This work emphasizes the importance of stromal SNAI2 in breast cancer progression and patients' prognosis.Item AMBRA1 regulates cyclin D to guard S-phase entry and genomic integrity(Nature, 2021) Maiani, Emiliano; Milletti, Giacomo; Nazio, Francesca; Holdgaard, Søs Grønbæk; Bartkova, Jirina; Rizza, Salvatore; Cianfanelli, Valentina; Lorente Pérez, María Del Mar; Simoneschi, Daniele; Di Marco, Miriam; D'Acunzo, Pasquale; Di Leo, Luca; Rasmussen, Rikke; Montagna, Costanza; Raciti, Marilena; De Stefanis, Cristiano; Gabicagogeascoa, Estíbaliz; Rona, Gergely; Salvador, Nélida; Pupo, Emanuela; Merchut-Maya, Joanna Maria; Daniel, Colin J.; Carinci, Marianna; Cesarin, Valeriana; O’sullivan, Alfie; Jeong, Yeon-Tae; Bordi, Matteo; Russo, Francesco; Campello, Silvia; Gallo, Angela; Filomeni, Giuseppe; Lanzetti, Letizia; Sears, Rosalie C.; Hamerlik, Petra; Bartolazzi, Armando; Hynds, Robert E.; Pearce, David R.; Swanton, Charles; Pagano, Michele; Velasco, Guillermo; Papaleo, Elena; Zio, Daniela De; Maya-Mendoza, Apolinar; Locatelli, Franco; Bartek, Jiri; Cecconi, FrancescoMammalian development, adult tissue homeostasis and the avoidance of severe diseases including cancer require a properly orchestrated cell cycle, as well as error-free genome maintenance. The key cell-fate decision to replicate the genome is controlled by two major signalling pathways that act in parallel—the MYC pathway and the cyclin D–cyclin-dependent kinase (CDK)–retinoblastoma protein (RB) pathway1,2. Both MYC and the cyclin D–CDK–RB axis are commonly deregulated in cancer, and this is associated with increased genomic instability. The autophagic tumour-suppressor protein AMBRA1 has been linked to the control of cell proliferation, but the underlying molecular mechanisms remain poorly understood. Here we show that AMBRA1 is an upstream master regulator of the transition from G1 to S phase and thereby prevents replication stress. Using a combination of cell and molecular approaches and in vivo models, we reveal that AMBRA1 regulates the abundance of D-type cyclins by mediating their degradation. Furthermore, by controlling the transition from G1 to S phase, AMBRA1 helps to maintain genomic integrity during DNA replication, which counteracts developmental abnormalities and tumour growth. Finally, we identify the CHK1 kinase as a potential therapeutic target in AMBRA1-deficient tumours. These results advance our understanding of the control of replication-phase entry and genomic integrity, and identify the AMBRA1–cyclin D pathway as a crucial cell-cycle-regulatory mechanism that is deeply interconnected with genomic stability in embryonic development and tumorigenesis.- Project number: PIMCD330/23-24
Item Evaluación por pares en asignaturas de Ingeniería Genética y Biología de Sistemas: de las herramientas digitales a la mentoría experta(2024) Sánchez Torralba, Antonio; Blázquez Ortiz, Cristina; Guevara Acosta, Govinda; Lorente Pérez, María Del Mar; López Conejo, María Teresa; Mateo Mendoza, Jorge Mario; Piedrafita Fernández, Gabriel; Ranz Valdecasas, Regina; Rayego Mateos, Sandra; Sánchez Velasco, Teresa; Navarro Llorens, Juana MaríaSe han introducido la evaluación por pares y la autoevaluación como herramientas promotoras del pensamiento crítico en el Laboratorio Integrado de Biofísica y Bioinformática, del Grado en Bioquímica, y en Fundamentos de Ingeniería Genética y Genómica, del Grado en Biología. En esta última, también se ha utilizado la ludificación para motivar al alumnado. Item Genetic manipulation of LKB1 elicits lethal metastatic prostate cancer(Journal of Experimental Biology, 2020) Hermanova, Ivana; Zuñiga-García, Patricia; Caro-Maldonado, Alfredo; Fernández Ruiz, Sonia; Salvador, Fernando; Martín-Martín, Natalia; Zabala-Letona, Amaia; Nuñez-Olle, Marc; Torrano, Verónica; Camacho, Laura; Lizcano, José M.; Talamillo, Ana; Carreira, Suzanne; Gure, Bora; Cortazar, Ana R.; Guiu, Marc; López, José I.; Martinez-Romero, Anabel; Astobiza, Ianire; Valcarcel-Jimenez, Lorea; Lorente Pérez, María Del Mar; Arruabarrena-Aristorena, Amaia; Velasco Díez, Guillermo; Gomez-Muñoz, Antonio; Suarez-Cabrera, Cristian; Lodewijk, Iris; Flores Landeira, Juana María; Sutherland, James D.; Barrio, Rosa; De Bono, Johann S.; Paramio, Jesús M.; Trka, Jan; Graupera, Mariona; Gomis, Roger R.; Carracedo, ArkaitzGene dosage is a key defining factor to understand cancer pathogenesis and progression, which requires the development of experimental models that aid better deconstruction of the disease. Here, we model an aggressive form of prostate cancer and show the unconventional association of LKB1 dosage to prostate tumorigenesis. Whereas loss of Lkb1 alone in the murine prostate epithelium was inconsequential for tumorigenesis, its combination with an oncogenic insult, illustrated by Pten heterozygosity, elicited lethal metastatic prostate cancer. Despite the low frequency of LKB1 deletion in patients, this event was significantly enriched in lung metastasis. Modeling the role of LKB1 in cellular systems revealed that the residual activity retained in a reported kinase-dead form, LKB1K78I, was sufficient to hamper tumor aggressiveness and metastatic dissemination. Our data suggest that prostate cells can function normally with low activity of LKB1, whereas its complete absence influences prostate cancer pathogenesis and dissemination.Item Midkine signaling maintains the self-renewal and tumorigenic capacity of glioma initiating cells(Theranostics, 2020) López Valero, Israel; Dávila, David; González Martínez, José; Salvador-Tormo, Nélida; Lorente Pérez, María Del Mar; Saiz Ladera, Cristina; Torres Pabón, Norma Sofía; Gabicagogeascoa Corta, Estíbaliz; Hernández-Tiedra, Sonia; García Taboada, Elena; Mendiburu Eliçabe, Marina; Rodríguez Fornés, Fátima; Sánchez Domínguez, Rebeca; Segovia Martínez, Juan Carlos; Sánchez Gómez, Pilar; Matheu Fernández, Ander; Sepúlveda Salas, Juan Miguel; Velasco Díez, GuillermoGlioblastoma (GBM) is one of the most aggressive forms of cancer. It has been proposed that the presence within these tumors of a population of cells with stem-like features termed Glioma Initiating Cells (GICs) is responsible for the relapses that take place in the patients with this disease. Targeting this cell population is therefore an issue of great therapeutic interest in neuro-oncology. We had previously found that the neurotrophic factor MIDKINE (MDK) promotes resistance to glioma cell death. The main objective of this work is therefore investigating the role of MDK in the regulation of GICs. Methods: Assays of gene and protein expression, self-renewal capacity, autophagy and apoptosis in cultures of GICs derived from GBM samples subjected to different treatments. Analysis of the growth of GICs-derived xenografts generated in mice upon blockade of the MDK and its receptor the ALK receptor tyrosine kinase (ALK) upon exposure to different treatments. Results: Genetic or pharmacological inhibition of MDK or ALK decreases the self-renewal and tumorigenic capacity of GICs via the autophagic degradation of the transcription factor SOX9. Blockade of the MDK/ALK axis in combination with temozolomide depletes the population of GICs in vitro and has a potent anticancer activity in xenografts derived from GICs. Conclusions: The MDK/ALK axis regulates the self-renewal capacity of GICs by controlling the autophagic degradation of the transcription factor SOX9. Inhibition of the MDK/ALK axis may be a therapeutic strategy to target GICs in GBM patients.- Project number: 306
Item La comunidad del anillo IGGIA: construyendo redes de mentoría en Ingeniería Genética mediante gamificación, internacionalización y accesibilidad(2022) Sánchez Torralba, Antonio; Benítez Prian, Mario; Blázquez Ortiz, Cristina; Bruñén Alfaro, Francisco; Cañadas Benito, Olga; García de la Camacha Selgas, Nuria; García-Fojeda García-Valdecasas, Belén; González Miranda, David; Guevara Acosta, Govinda; López Conejo, María Teresa; Lorente Pérez, María Del Mar; Mateo Mendoza, Jorge Mario; Nogués Vera, Laura; Raisman, Andrea; Ranz Valdecasa, María Regina; Ruiz Ortega, Marta; Sánchez-Escalonilla Relea, Jose Luis; Sánchez Velasco, Teresa; Toledo Marcos, Juan; Velasco Díez, Guillermo; Navarro Llorens, Juana María - Project number: 163
Item The Phantom Menace: Cómo salvar el mundo de una pandemia mediante Ingeniería Genética cooperativa(2021) Navarro Llorens, Juana María; Baldanta Callejo, Sara; Bénitez Prian, Mario; Blázquez Ortiz, Cristina; Bruñen Alfaro, Francisco; Cañadas Benito, Olga; Chinarro Sánchez, Adrián; García de la Camacha Selgas, Nuria; García-Fojeda García-Valdecasas, María Belén; Guevara Acosta, Flor Govinda; Leaño Hinojosa, Ariana; López Conejo, Maria Teresa; Lorente Pérez, María Del Mar; Nogués Vera, Laura; Penalba Iglesias, Diana; Raisman, Andrea; Ranz Valdecasa, Maria Regina; Ruiz Ortega, Marta; Sánchez-Escalonilla Relea, Jose luis; Velasco Díez, Guillermo; Sánchez Torralba, AntonioEl año pasado se llevó a cabo un proyecto de innovación (PIMCD-2019 174) basado en el modelo pedagógico de la clase invertida o “Flipped Classroom” y en el juego de mesa PANDEMIC (ASMODEE IBÉRICA). Brevemente, este proyecto consistió en una propuesta didáctica sobre los contenidos de FIGG en el que tomando como partida un entorno lúdico, los alumnos de FIGG en equipos preparaban contenidos y reforzaban conocimientos adquiridos en clase. Para llevarlo a cabo, a los alumnos se les planteaba una hipotética situación en la que cuatro enfermedades mortales aparecen en la tierra. Los alumnos divididos en equipos de 5 personas, deben cooperar desarrollando una serie de acciones que les permitan ir conociendo a qué patógeno se enfrentan y desarrollar herramientas que les permita controlar la epidemia dentro de un tiempo dado. Así cada equipo debe frenar el avance de las infecciones y a la vez encontrar una cura para la misma. Curiosamente, todo este escenario fue planteado antes de que la crisis del COVID-19 impactara en nuestra sociedad. En cualquier caso, la situación vivida en los últimos meses ha motivado a los estudiantes de FIGG por lo que en su mayor parte han participado en su desarrollo de manera entusiasta. En este nuevo proyecto, hemos tomado como base el proyecto del curso pasado, pero introduciendo algunos elementos innovadores. Entre estas innovaciones destaca la incorporación de dos alumnos por grupo de FIGG que ya lo hubieran realizado en la edición pasada por cada uno de los grupos de FIGG como mentores. - Project number: 225
Item H5P-Pandemic: Motivando al alumnado mediante ejercicios interactivos ludificados en asignaturas de ingeniería genética(2023) Sánchez Torralba, Antonio; Lorente Pérez, María Del Mar; Blázquez Ortiz, Cristina; Velasco Díez, Guillermo; Ranz Valdecasas, Mª Regina; López Conejo, Mª Teresa; García-Fojeda García-Valdecasas, Mª Belén; Nogués Vera, Laura; Cañadas Benito, Olga; Guevara Acosta, Flor Govinda; Ruiz Ortega, Marta; Rayego Mateos, Sandra; Sánchez Velasco, Teresa; Mateo Mendoza, Jorge Mario; Navarro Llorens, Juana MaríaFundamentos de Ingeniería Genética y Genómica (Grado en Biología) se ludificó con éxito mediante un juego de pandemias. Se ha mejorado la participación y el autoaprendizaje del alumnado con ejercicios autoevaluables de tipo H5P y exportables a Moodle. - Project number: 174
Item PANDEMIC: Cómo salvar el mundo mediante Ingeniería Genética cooperativa(2020) Navarro Llorens, Juana María; Lorente Pérez, María Del Mar; Blázquez Ortiz, Cristina; Ranz Valdecasa, Regina; López Conejo, María Teresa; García-Fojeda García-Valdecasas, María Belén; Cañadas Benito, Olga; Castillo-Lluva, Sonia; Velasco Díez, Guillermo; Guevara Acosta, Flor Govinda; Sánchez Torralba, AntonioProyecto de Innovación llevado a cabo en la UCM, grado de Biología para el aprendizaje de técnicas de ingeniería genética. Se ha dividido a los alumnos en equipos y se realizado una gamificación de la asignatura basado en el juego de mesa de Pandemic. Brevemente, cada equipo se enfrenta a una enfermedad desconocida y en cada tema adquiere las competencias necesarias para caracterizar al patógeno, conocer su genoma y acabar obteniendo una vacuna contra el agente.