CHARACTERIZATION OF E3 UBIQUITIN LIGASE HERC1 AS AN IMPORTANT REGULATOR OF TUMOR CELL INVASION AND MIGRATION

JULIANA ENRIQUÉ STEINBERG; EZEQUIEL CALVO-ROITBERG; JOAQUIN M ESPINOSA; FABIANA ALEJANDRA ROSSI; MARIO ROSSI

Congreso; Reunión Conjunta de Sociedades de Biociencias 2017; 2017

Despite formidable advance in the prevention, early detection and treatment of a great number of cancers, the development of metastasis represents the principal cause of death in patients with solid tumors. The invasive potential of malignant cells is characterized by a series of molecular and genetic modifications that increase their invasive potential, allowing them to penetrate the extracellular matrix and spread in the surrounding tissues. These changesare associated with alterations in a wide variety of posttranslational modification patterns, including the Ubiquitin-Proteasome System (UPS). The UPS plays a fundamental role in almost every single cellular process, and therefore it is not surprising that genetic alterations, abnormal expression or dysfunction of different components of this cascade are often associated with malignant transformation of tumor cells and the development of metastatic processes. Using shRNAs that target different UPS genes we identified Herc1as a key player in the control of tumor cell migration and invasion. Herc1 is a huge protein involved in intracellular membranes trafficking and its role in the control of the metastatic capability of tumor cells has not been reported yet. Using different phenotypic experiments, such as Boyden chamber, proliferation, wound healing and colony formation assays we were able to demonstrate that the depletion of Herc1 decreases the invasiveness of triple negative cancercells, highlighting its potential as a novel putative therapeutic candidate for cancer treatment.