https://hdl.handle.net/10259/12236 2026-10-07T23:37:30Z https://hdl.handle.net/10259/12245 Toxicologial Evaluation of Pristine MXene, PolyPyrrole Functionalized MXene, and MXene-Graphene Hybrids Using Cellular and Computational Models Fuente Vivas, Dalia de la; Huerta Sainz, Sergio de la; Rodriguez-Vinagre, J.; Palacios Santamaría, David; Aparicio Martínez, Santiago; Gómez Cuadrado, Laura Background: MXenes and Graphene possess outstanding physicochemical properties (thermal stability, electrical conductivity). They have strong application potential in biosensors, conductive ink, and EMI shielding. Challenge: Current (nano)particle regulations present critical gaps, particularly in human health risk assessment. There is a growing need for Safe by Design (SbD) aligned evaluation strategies. Aim: Implementing NAMs (in vitro and in silico) to replace animal testing and effectively bridge the in vitro-in vivo gap in safety assessments. Approach: Step-1 SbD was implemented via chemical hazard identification. In vitro NAMs (static and dynamic 3D spheroids) were compared with 2D cultures in a multi-tiered approach integrating toxicological profiles with predictive in silico models for mechanistic cellular analysis. Impact: Enables SbD-driven, animal-free predictive toxicology by integrating advanced 3D NAMs with in silico mechanistic modeling. Póster presentado a: 23 International Congress ESTIV, Maastricht, 2026, 29 june - 2 july 2026-01-01T00:00:00Z https://hdl.handle.net/10259/12244 Scaffold proteins and cytoskeletal dynamics as modulators of Ras-ERK pathway in cancer Fuente Vivas, Dalia de la; Casar, Berta; Crespo, Pedro An overwhelming body of data unquestionably links the Ras-ERK pathway to the upbringing and progression of human malignancies. About 40% of human cancers harbor activating mutations in proteins involved in this signaling cascade, in particular Ras and Braf. In addition to the main proteins of this signaling pathway, there are several regulatory proteins known as scaffold proteins, that modulate the intensity, amplitude and duration of ERK signals. Interestingly, it can propose the scaffold proteins as antitumoral targets. Considering the hypothesis that scaffold proteins interact and regulate the signal transduction through the Ras-ERK pathway in a coordinated manner we try to find out how these interactions are regulated. Ras proteins are distributed in different types of plasma membrane: microdomains and endomembranes. We have previously demonstrated that compartmentalization dictates Ras utilization of effectors, the intensity of its signals and the biological response of the cells. Cell migration is critical for many physiological processes and is often misregulated in developmental disorders and pathological conditions including cancer. MAPK signaling are known regulators of cytoskeletal dynamics during cellular processes such as cell adhesion and migration. Our hypothesis is that localized ERK signaling mediated through recently identified scaffold proteins and its interactions with the cytoskeleton may regulate specific cellular responses. Here we propose that associations among different scaffold proteins and cytoskeleton will add one further degree of regulation for an already tightly regulated cascade and could provide a novel means for manipulating ERK signals, even with therapeutic purposes. Póster presentado en: 41 Congreso de la SEBBM, Santander, 10-13 septiembre 2018 2018-01-01T00:00:00Z https://hdl.handle.net/10259/12242 SWI/SNF alterations in cancer: molecular targets and therapeutic implications Monteverde, Beatriz; Moreno, Thaidy; Fuente Vivas, Dalia de la; Revilla, Carlos; Casar, Berta; Crespo, Piero; Varela, Ignacio Background: SWI/SNF chromatin remodelling complex is altered in nearly 20% of all human tumor types, which places it as the most broadly mutated molecular system in human cancer, just after TP53 [1, 2]. Nevertheless, the molecular mechanisms through which these alterations foster cancer development remain to be fully understood. In addition, any potential susceptibility associated with SWI/SNF alterations might be exploited for the treatment of patients affected by different malignancies. Methodology: We have generated stably-transduced cell lines for a doxycycline-inducible vector that directs the expression of different shRNAs targeting ARID1A, ARID1B or ARID2 in different human cancer cell lines. We have studied the transcriptional alterations resulted from the deficiency of these subunits in different cellular contexts by RNA-Seq, as well as the changes in chromatin accessibility by ATAC-Seq. Additionally, we have studied the sensitivity of these cell lines to different antitumoral treatments. Results: We have identified molecular pathways differently expressed in the SWI/SNF-deficient cell lines that might explain some characteristics of the behaviour of these tumor cells. Thus, we have seen an overexpression of genes involved in ROS production, as well as genes encoding metallopeptidases, and a downregulation of genes related to cellular adhesion or tumor suppression. Finally, we have detected different sensitivities in the ARID-deficient cells to some treatments, like cis-platin, and PARP or EGFR inhibitors. Póster presentado en: 42 Congress SEBBM, Madrid, 16-19 july 2019 2019-01-01T00:00:00Z https://hdl.handle.net/10259/12239 ERK dimerization promotes migration and invasion Fuente Vivas, Dalia de la; Casar, Berta; Crespo, Piero Activation of the Ras-ERK signaling cascade is associated with increased metastasis risk inbreast cancer. In the present study. ERK dimerization plays a crucial role in the migrationand invasion of breast tumor cells. ERK dimers bind to the scaffold protein KSR1 toenhance migration. Blocking ERK dimers formation reduced invasion capacity of MCF-7and MDA-231-MB tumors cells. Thus, targeting ERK dimerization could emerge as a validtherapeutic strategy for the treatment of breast cancer. Póster presentado en: EACR 2021 Virtual Congress, 9-12 June 2021 2021-01-01T00:00:00Z