Person: Castillo Lluva, Sonia
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First Name
Sonia
Last Name
Castillo Lluva
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Ciencias Químicas
Department
Bioquímica y Biología Molecular
Area
Bioquímica y Biología Molecular
Identifiers
15 results
Search Results
Now showing 1 - 10 of 15
- Project number: 17
Item ¿Qué es lo que sabemos… sobre Biología? IV() Aguado Sánchez, Tania; Batanero Cremades, Eva; Castillo Lluva, Sonia; García Álvarez, Begoña; Palazuelos Diego, Javier; Pérez Gómez, Eduardo; Sánchez García, Cristina; Yélamos López, María BelénEl inglés y las tecnologías móviles son fundamentales hoy día. Los estudiantes utilizarán dichas tecnologías para motivar y reforzar el aprendizaje de Biología mediante dos actividades: crear cuestionarios Kahoot! en inglés y emplearlos en concursos. - Project number: 8
Item ¿Qué es lo que sabemos… sobre Biología?(2021) Batanero Cremades, Eva; Rodríguez Crespo, José Ignacio; Castillo Lluva, Sonia; García Álvarez, Begoña; Bueno Díaz, CristinaDada la importancia del inglés y de las tecnologías móviles hoy día, los estudiantes utilizarán dichas tecnologías para reforzar el aprendizaje de Biología, y motivarlos a estudiar, mediante dos actividades: crear test Kahoot! en inglés y concursar. Item Mechanistic insights into the antitumoral potential and in vivo antiproliferative efficacy of a silver-based core@shell nanosystem(International Journal of Pharmaceutics, 2024) Aragoneses Cazorla, Guillermo; Álvarez-Fernández García, Roberto; Martínez López, Angelica; Gómez Gómez, María Milagros; Vallet Regí, María Dulce Nombre; Castillo Lluva, Sonia; González Ortiz, Blanca; Luque García, José LuisThis study delves into the biomolecular mechanisms underlying the antitumoral efficacy of a hybrid nanosystem, comprised of a silver core@shell (Ag@MSNs) functionalized with transferrin (Tf). Employing a SILAC proteomics strategy, we identified over 150 de-regulated proteins following exposure to the nanosystem. These proteins play pivotal roles in diverse cellular processes, including mitochondrial fission, calcium homeostasis, endoplasmic reticulum (ER) stress, oxidative stress response, migration, invasion, protein synthesis, RNA maturation, chemoresistance, and cellular proliferation. Rigorous validation of key findings substantiates that the nanosystem elicits its antitumoral effects by activating mitochondrial fission, leading to disruptions in calcium homeostasis, as corroborated by RT-qPCR and flow cytometry analyses. Additionally, induction of ER stress was validated through western blotting of ER stress markers. The cytotoxic action of the nanosystem was further affirmed through the generation of cytosolic and mitochondrial reactive oxygen species (ROS). Finally, in vivo experiments using a chicken embryo model not only confirmed the antitumoral capacity of the nanosystem, but also demonstrated its efficacy in reducing cellular proliferation. These comprehensive findings endorse the potential of the designed Ag@MSNs-Tf nanosystem as a roundbreaking chemotherapeutic agent, shedding light on its multifaceted mechanisms and in vivo applicability.- Project number: 7
Item ¿Qué es lo que sabemos…sobre Biología III?() Batanero Cremades, Eva; Castillo Lluva, Sonia; García Álvarez, Begoña; Pérez Gómez, Eduardo; Yélamos López, María BelénEl inglés y las tecnologías móviles son fundamentales hoy día. Los estudiantes utilizarán dichas tecnologías para motivar y reforzar el aprendizaje de Biología mediante dos actividades: crear cuestionarios Kahoot! en inglés y emplearlos en concursos. Item Evolutionary Origins of Metabolic Reprogramming in Cancer(2022) García-Sancha, Natalia; Corchado-Cobos, Roberto; Gómez-Vecino, Aurora; Jiménez-Navas, Alejandro; Pérez-Baena, Manuel Jesús; Blanco-Gómez, Adrián; Holgado-Madruga, Marina; Jian-Hua, Mao; Cañueto, Javier; Castillo Lluva, Sonia; Mendiburu-Eliçabe Garganta, Marina; Pérez-Losada, JesúsMetabolic changes that facilitate tumor growth are one of the hallmarks of cancer. These changes are not specific to tumors but also take place during the physiological growth of tissues. Indeed, the cellular and tissue mechanisms present in the tumor have their physiological counterpart in the repair of tissue lesions and wound healing. These molecular mechanisms have been acquired during metazoan evolution, first to eliminate the infection of the tissue injury, then to enter an effective regenerative phase. Cancer itself could be considered a phenomenon of antagonistic pleiotropy of the genes involved in effective tissue repair. Cancer and tissue repair are complex traits that share many intermediate phenotypes at the molecular, cellular, and tissue levels, and all of these are integrated within a Systems Biology structure. Complex traits are influenced by a multitude of common genes, each with a weak effect. This polygenic component of complex traits is mainly unknown and so makes up part of the missing heritability. Here, we try to integrate these different perspectives from the point of view of the metabolic changes observed in cancer.Item Inhibition of RAC1 activity in cancer associated fibroblasts favours breast tumour development through IL-1β upregulation(Cancer Letters, 2021) Martínez López, Angélica; García Casas, Ana; Bragado Domingo, Paloma; Orimo, Akira; Castañeda-Saucedo, Eduardo; Castillo Lluva, SoniaCancer-associated fibroblasts (CAFs) are highly abundant stromal components in the tumour microenvironment. These cells contribute to tumorigenesis and indeed, they have been proposed as a target for anti-cancer therapies. Similarly, targeting the Rho-GTPase RAC1 has also been suggested as a potential therapeutic target in cancer. Here, we show that targeting RAC1 activity, either pharmacologically or by genetic silencing, increases the pro-tumorigenic activity of CAFs by upregulating IL-1β secretion. Moreover, inhibiting RAC1 activity shifts the CAF subtype to a more aggressive phenotype. Thus, as RAC1 suppresses the secretion of IL-1β by CAFs, reducing RAC1 activity in combination with the depletion of this cytokine should be considered as an interesting therapeutic option for breast cancer in which tumour cells retain intact IL-1β signalling..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 Intermediate Molecular Phenotypes to Identify Genetic Markers of Anthracycline-Induced Cardiotoxicity Risk(Cells, 2023) Gómez Vecino, Aurora; Corchado Cobos, Roberto; Blanco Gómez, Adrián; García Sancha, Natalia; Martín García, Ana ; Mendiburu-Eliçabe Garganta, Marina; Prieto, Carlos; Ruiz Pinto, Sara; Pita, Guillermo; Velasco Ruiz, Alejandro; Patino Alonso, Carmen; Galindo Villardón, Purificación; Linarejos Vera Pedrosa, María; Jalife, José; Mao, Jian-Hua; Macías de Plasencia, Guillermo ; Castellanos Martín, Andrés ; Sáez Freire, María del Mar; Fraile Martín, Susana ; Rodrigues Teixeira, Telmo ; García Macías, Carmen ; Galvis Jiménez, Julie Milena ; Castillo Lluva, Sonia; García Sánchez, Asunción ; Isidoro García, María; Fuentes, Manuel ; García Cenador, María Begoña ; García Criado, Francisco Javier ; García Hernández, Juan Luis; Hernández García, María Ángeles ; Cruz Hernández, Juan Jesús ; Rodríguez Sánchez, César Augusto ; Martín García-Sancho, Alejandro ; Pérez López, Estefanía ; Pérez Martínez, Antonio ; Gutiérrez Larraya, Federico; Cartón, Antonio J.; García Sáenz, José Ángel; Patiño-García, Ana; Martín, Miguel; Alonso Gordoa, Teresa; Vulsteke, Christof ; Croes, Lieselot ; Hatse, Sigrid ; Van Brussel, Thomas ; Lambrechts, Diether ; Wildiers, Hans ; Hang, Chang ; Holgado Madruga, Marina; González-Neira, Anna; Sánchez, Pedro L.; Pérez Losada, JesúsCardiotoxicity due to anthracyclines (CDA) affects cancer patients, but we cannot predict who may suffer from this complication. CDA is a complex trait with a polygenic component that is mainly unidentified. We propose that levels of intermediate molecular phenotypes (IMPs) in the myocardium associated with histopathological damage could explain CDA susceptibility, so variants of genes encoding these IMPs could identify patients susceptible to this complication. Thus, a genetically heterogeneous cohort of mice (n = 165) generated by backcrossing were treated with doxorubicin and docetaxel. We quantified heart fibrosis using an Ariol slide scanner and intramyocardial levels of IMPs using multiplex bead arrays and QPCR. We identified quantitative trait loci linked to IMPs (ipQTLs) and cdaQTLs via linkage analysis. In three cancer patient cohorts, CDA was quantified using echocardiography or Cardiac Magnetic Resonance. CDA behaves as a complex trait in the mouse cohort. IMP levels in the myocardium were associated with CDA. ipQTLs integrated into genetic models with cdaQTLs account for more CDA phenotypic variation than that explained by cda-QTLs alone. Allelic forms of genes encoding IMPs associated with CDA in mice, including AKT1, MAPK14, MAPK8, STAT3, CAS3, and TP53, are genetic determinants of CDA in patients. Two genetic risk scores for pediatric patients (n = 71) and women with breast cancer (n = 420) were generated using machine-learning Least Absolute Shrinkage and Selection Operator (LASSO) regression. Thus, IMPs associated with heart damage identify genetic markers of CDA risk, thereby allowing more personalized patient management.Item Inhibiting SUMO1-mediated SUMOylation induces autophagy-mediated cancer cell death and reduces tumour cell invasion via RAC1(Journal of Cell Science, 2019) Lorente Pérez, María Del Mar; García-Casas, Ana; Salvador, Nélida; Martínez-López, Angélica; Gabicagogeascoa, Estíbaliz; Velasco, Guillermo; López-Palomar, Lucía; Castillo Lluva, SoniaPost-translational modifications directly control protein activity and thus, they represent an important means to regulate the responses of cells to different stimuli. Protein SUMOylation has recently been recognised as one such modification and it has been associated with various diseases, including different types of cancer. However, the precise way that changes in SUMOylation influence the tumourigenic properties of cells remains to be fully clarified. Here, we show that blocking the SUMO pathway by depleting SUMO1 and UBC9, or by exposure to Ginkgolic acid C15:1 or 2-D08 (two different SUMOylation inhibitors), induces cell death, also inhibiting the invasiveness of tumour cells. Indeed, diminishing the formation of SUMO1 complexes induces autophagymediated cancer cell death by increasing the expression of Tribbles pseudokinase 3. Moreover, we found that blocking the SUMO pathway inhibits tumour cell invasion by decreasing RAC1 SUMOylation. These findings shed new light on the mechanisms by which SUMO1 modifications regulate the survival, and the migratory and invasive capacity of tumour cells, potentially establishing the bases to develop novel anti-cancer treatments based on the inhibition of SUMOylation.Item Lung Surfactant Lipids Provide Immune Protection Against Haemophilus influenzae Respiratory Infection(Frontiers in Immunology, 2019) García-Fojeda, Belén; González-Carnicero, Zoe; Lorenzo Avilés, Alba de; Minutti, Carlos M.; Tapia, Lidia de; Euba, Begoña; Iglesias-Ceacero, Alba; Castillo Lluva, Sonia; Garmendia, Junkal; Casals Carro, María CristinaNon-typeable Haemophilus influenzae (NTHi) causes persistent respiratory infections in patients with chronic obstructive pulmonary disease (COPD), probably linked to its capacity to invade and reside within pneumocytes. In the alveolar fluid, NTHi is in contact with pulmonary surfactant, a lipoprotein complex that protects the lung against alveolar collapse and constitutes the front line of defense against inhaled pathogens and toxins. Decreased levels of surfactant phospholipids have been reported in smokers and patients with COPD. The objective of this study was to investigate the effect of surfactant phospholipids on the host-pathogen interaction between NTHi and pneumocytes. For this purpose, we used two types of surfactant lipid vesicles present in the alveolar fluid: (i) multilamellar vesicles (MLVs, > 1 μm diameter), which constitute the tensioactive material of surfactant, and (ii) small unilamellar vesicles (SUVs, 0.1 μm diameter), which are generated after inspiration/expiration cycles, and are endocytosed by pneumocytes for their degradation and/or recycling. Results indicated that extracellular pulmonary surfactant binds to NTHi, preventing NTHi self-aggregation and inhibiting adhesion of NTHi to pneumocytes and, consequently, inhibiting NTHi invasion. In contrast, endocytosed surfactant lipids, mainly via the scavenger receptor SR-BI, did not affect NTHi adhesion but inhibited NTHi invasion by blocking bacterial uptake in pneumocytes. This blockade was made possible by inhibiting Akt phosphorylation and Rac1 GTPase activation, which are signaling pathways involved in NTHi internalization. Administration of the hydrophobic fraction of lung surfactant in vivo accelerated bacterial clearance in a mouse model of NTHi pulmonary infection, supporting the notion that the lipid component of lung surfactant protects against NTHi infection. These results suggest that alterations in surfactant lipid levels in COPD patients may increase susceptibility to infection by this pathogen.