Person:
Castillo Lluva, Sonia

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First Name
Sonia
Last Name
Castillo Lluva
URI
https://hdl.handle.net/20.500.14352/76241
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Ciencias Químicas
Department
Bioquímica y Biología Molecular
Area
Bioquímica y Biología Molecular
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2019 - 201912020 - 20241
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Author: Salvador, Nélida × Subject: 577.2 ×

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Now showing 1 - 2 of 2
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    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, Sonia
    Post-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.
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    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, Jesús
    Background: 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.