PIF2024 - METASTASIS Y DIETA ALTA EN GRASAS (PID2023-152426OA-I00)

Breast cancer, primarily affecting women, is the most common cancer, with metastasis responsible for most deaths. Currently, no effective treatment exists, making it crucial to understand the mechanisms behind metastasis for better control. Diet-induced obesity, a major risk factor for poor prognosis, is common in breast cancer patients. Research has focused on how metastatic cells use fat-derived metabolites, and we have discovered that breast cancer cells use palmitate to activate pro-metastatic signaling for lung colonization. However, the effect of diet, particularly palmitate, on the recipient tissue's susceptibility to metastasis is still unknown. Intriguingly, our preliminary data reveals that a high-fat diet induces metabolic changes in the lung, characterized by elevated glutamate levels. Moreover, breast cancer metastatic cells exploit this primed glutamate, facilitating their growth, yet the underlying mechanisms remain unexplored. This project seeks to fill this gap by exploring (i) how fat-priming boosts glutamate in the niche, (ii) interactions between metastatic cells and the fat-primed environment, and (iii) strategies to prevent metastasis by targeting diet-priming. Using multi-omics, molecular biology, mass spectrometry, and in vivo models, we aim to uncover key insights into using dietary changes as a strategy to combat metastasis.