shRNA screen for ubiquitination genes involved in tumor-cell invasion and migration regulation

FABIANA A. ROSSI; JOAQUIN M. ESPINOSA; JULIANA H. ENRIQUÉ STEINBERG ; MARIO ROSSI; EZEQUIEL CALVO-ROITBERG

Galveston

Conferencia; Gordon Research Conference: Directed cell migration; 2017

Gordon Research Conferences

Despite formidable advance in the prevention, early detection and treatment of a great number of cancers, the development of metastasis foci in patients suffering from this disease still represents a significant reduction in their survival and life quality. Although metastatic cells have partially been characterized, there is yet not an effective treatment for this pathological condition. The Ubiquitin-Proteasome System (UPS) plays a fundamental role in the maintenance of protein homeostasis both in normal and stressed conditions. This enzymatic cascade represents one of the most important metabolic protein degradation pathways and plays a fundamental role in the control of almost every single cellular process. Since alterations in the ubiquitination cascade have been shown to be associated with malignant transformation, invasive potential of cells and metastasis, we sought to investigate the role of the UPS in the regulation of tumor-cell invasion and migration. We performed 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 non-migrating populations of cells were characterized and the shRNA present in them were determined.