Role of protein ubiquitylation in regulating tumor-cell invasion and migration

FABIANA ROSSI; JULIANA ENRIQUÉ STEINBERG; JOAQUIN M ESPINOSA; MARIO ROSSI

Rosario

Congreso; L Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2014

Metastatic disease is the most common cause of cancer-related death in patients with solid tumors. A considerable body of evidence indicates that tumor cells are shed from a primary tumor mass at the earliest stages of malignant progression, and that the invasive potential of these determines, to some extent, the aggressiveness of newly formed secondary tumors. Despite characterizations on metastatic cells, there is yet not an effective treatment for this disease. Ubiquitylation is a post translational modification that has recently became of great interest due to its therapeutic potential regarding cancer treatment. Alterations in the ubiquitylation cascade have been shown to be associated with malignant transformation, invasive potential of cells and metastasis. Hence, we sought to investigate the role of the Ubiquitin Proteasome System (UPS) in the regulation of tumor-cell invasion and migration. In order to find new UPS genes that are related to invasion and migration, we set out to perform a genetic screen using a shRNA library against UPS genes, and Boyden chambers to analyze the migrating/invasive potential of cells infected with this library. After the selection process, the relative abundance of the shRNA present in the different isolated populations will be assessed by next generation sequencing and the putative candidates will be further validated in vivo.