PIF2025 - INTERACTOMA Y PLASTICIDAD CELULAR EN EVOLUCION TUMORAL Y POTENCIAL METASTASICO - (PID2024-155973NB-I00)

Cell plasticity in health and disease is behind cell differentiation, and most importantly, behind tissue repair, degeneration and cancer (Nieto et al, Cell 2016; Youssef & Nieto, Nature Rev Cell Mol Biol 2024). Cell plasticity is a property by which cells change their phenotype in response to external stimuli, either physiological or pathological to fulfill a specific function or to maintain homeostasis. When pathological stimuli become chronic, the tissue cannot be repaired and degenerates. Our purpose is to advance in our knowledge of the mechanisms driving cell plasticity in cancer. Recently, we have shown that cancer cells dedifferentiate and adopt one of two opposing plasticity trajectories: an embryonic-like path that promotes metastasis or an adult-like path that fosters anti-tumour inflammation (Youssef et al, Nature Cancer, 2024). The balance between these two opposing trajectories can determine cancer progression and patient outcome. Our goal is to study the interactions between cancer cells and stromal populations in breast cancer models along the two described trajectories. Single cell transcriptomics, chromatin structure and computational analysis of cell-cell interactions plus spatial transcriptomics will allow us to describe functional interactions and the associated signalling pathways. Revealing interconnected pro-tumour and anti-tumour responses will uncover novel targets to guide therapeutic strategies, ultimately aiming at improving clinical outcomes.