Targeting post prenylation processing in cancer: study of the role of ICMT in tumor progression

BORINI CARLA; DI BENEDETTO CAROLINA; ROSSI CAROLINA; GIRARDINI J.

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Most human cancers inactivate the tumor suppressor p53 through missense mutations, leading to the abundant expression of full-length point mutant proteins. p53 mutants not only lose the tumor suppressor function but may also acquire novel activities that promote tumor progression. Despite evidences showing that mutant p53 enhances tumor aggressiveness, the mechanisms underlying this activity are still poorly understood. We focused on ICMT, which regulates subcellular localization and function of proteins with a C-terminal CaaX motif, including members of the RHO family, by catalyzing post-prenilation carboximethylation. Our results also showed that ICMT enhances human tumor cell clonogenic potential in vitro and tumor formation in vivo in nude mice. By using three dimensional cultures we found that ICMT is able to disrupt epithelial architecture, suggesting a role in the acquisition of aggressive traits. Collectively, our data shows that ICMT deregulation cooperates with the acquisition of aggressive phenotypes.