Metastasis is the primary cause of cancer-related deaths, yet the biological processes that enable tumor cells to spread, survive in distant organs, and eventually form secondary tumors remain incompletely understood. Gaining insight into these mechanisms is essential for developing strategies to prevent and treat metastatic disease across cancer types.

In the first part of my presentation, I will discuss tumour dormancy in breast cancer. To uncover regulators of dormancy, genome-wide CRISPR screens were performed on two breast cancer cell lines: 4T1 (short dormancy) and 4T07 (prolonged dormancy). 4T07 cells uniquely depended on class III PI3K (PIK3C3) and showed elevated mTORC1 activity via peripheral lysosome signaling. Inhibiting PIK3C3 suppressed this activity in both mouse and human models, reduced metastasis in 4T07, and eliminated dormant cells in a HER2-driven model. These results highlight PIK3C3-mTORC1 signaling as a potential therapeutic target to prevent metastatic relapse. In the second part of the presentation, I will focus on RAS family proteins that regulates key signaling pathways involved in cell growth, differentiation, and survival. While canonical RAS proteins are well studied, the broader group of 35 human RAS-related GTPases remains largely unexplored. Using proximity-dependent biotinylation (BioID) in three cell models, we mapped interaction networks and subcellular localizations across the family. This generated a high-confidence interactome, revealing thousands of spatially resolved associations. By analyzing nucleotide-state-specific variants, we identified context-dependent interactions with effectors and regulators. Comparative clustering highlighted conserved and unique features across subfamilies. Integration with DepMap data uncovered essential crosstalk with regulators Rho GTPases and cytoskeletal dynamics in canonical RAS proteins. This resource advances our understanding of RAS-family signaling and its roles in development, disease, and cancer.