Person: Castillo Lluva, Sonia
Loading...
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
3 results
Search Results
Now showing 1 - 3 of 3
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.Item NCAPH drives breast cancer progression and identifies a gene signature that predicts luminal a tumour recurrence(Clinical and translational medicine, 2024) Mendiburu-Eliçabe Garganta, Marina; García‐Sancha, Natalia; Corchado‐Cobos, Roberto; Martínez‐López, Angélica; Chang, Hang; Mao, Jian Hua; Blanco‐Gómez, Adrián; García Casas, Ana; Castellanos‐Martín, Andrés; Salvador, Nélida; Jiménez‐Navas, Alejandro; Pérez‐Baena, Manuel Jesús; Sánchez‐Martín, Manuel Adolfo; Abad‐Hernández, María Del Mar; Carmen, Sofía Del; Claros‐Ampuero, Juncal; Cruz‐Hernández, Juan Jesús; Rodríguez‐Sánchez, César Augusto; García‐Cenador, María Begoña; García‐Criado, Francisco Javier; Santamaría Vicente, Rodrigo; Castillo Lluva, Sonia; Pérez‐Losada, JesúsBackground: Luminal A tumours generally have a favourable prognosis but possess the highest 10‐year recurrence risk among breast cancers. Additionally, a quarter of the recurrence cases occur within 5 years post‐diagnosis. Identifying such patients is crucial as long‐term relapsers could benefit from extended hormone therapy, while early relapsers might require more aggressive treatment. Methods: We conducted a study to explore non‐structural chromosome maintenance condensin I complex subunit H’s (NCAPH) role in luminal A breast cancer pathogenesis, both in vitro and in vivo, aiming to identify an intratumoural gene expression signature, with a focus on elevated NCAPH levels, as a potential marker for unfavourable progression. Our analysis included transgenic mouse models overexpressing NCAPH and a genetically diverse mouse cohort generated by backcrossing. A least absolute shrinkage and selection operator (LASSO) multivariate regression analysis was performed on transcripts associated with elevated intratumoural NCAPH levels. Results: We found that NCAPH contributes to adverse luminal A breast cancer progression. The intratumoural gene expression signature associated with elevated NCAPH levels emerged as a potential risk identifier. Transgenic mice overexpressing NCAPH developed breast tumours with extended latency, and in Mouse Mammary Tumor Virus (MMTV)‐NCAPH ErbB2 double‐transgenic mice, luminal tumours showed increased aggressiveness. High intratumoural Ncaph levels correlated with worse breast cancer outcome and subpar chemotherapy response. A 10‐gene risk score, termed Gene Signature for Luminal A 10 (GSLA10), was derived from the LASSO analysis, correlating with adverse luminal A breast cancer progression. Conclusions: The GSLA10 signature outperformed the Oncotype DX signature in discerning tumours with unfavourable outcomes, previously categorised as luminal A by Prediction Analysis of Microarray 50 (PAM50) across three independent human cohorts. This new signature holds promise for identifying luminal A tumour patients with adverse prognosis, aiding in the development of personalised treatment strategies to significantly improve patient outcomes.