ROLE OF KRIT1 IN THE ACQUISITION OF AGGRESSIVE PHENOTYPE IN CANCER CELLS

K-Rev Interaction Trapped protein-1 (KRIT1) is a scaffold protein known to form functional protein complexes involved in physiologically important signaling networks. While it is primarily recognised for its association with Cerebral Cavernous Malformations (CCMs), KRIT1 also plays critical roles in tumor formation and the acquisition of malignant phenotypes. These roles include functions in cell adhesion, cytoskeletal dynamics, and angiogenesis. The present study investigates the involvement of KRIT1 in tumor progression and plasticity. The research focused on the potential tumor-suppressor-like properties of KRIT1, particularly in relation to invasion and migration processes. Notably, KIF1C and NS1A have been identified as novel binding partners of KRIT1. KIF1C plays a crucial role in regulating podosomes and invadopodia elongation, while NS1A contributes to the organization of the actin cytoskeleton dynamics by stabilizing actin filaments through its association with F-actin. The role of KRIT1 in tumour invasion and migration was evaluated both in vitro and in vivo. Additionally, the impact of KRIT1 loss on SRC, FAK, and RhoA/ROCK signaling pathways, as well as its involvement in cytoskeleton dynamics, was analysed. The findings of this study corroborate the role of KRIT1 as a tumor suppressor gene and reveal a correlation between its depletion and increased cancer aggressiveness.