HERC1 Regulates Breast Cancer Cells Migration and Invasion
Instituto de Medicina Traslacional (IIMT), CONICET-Universidad Austral, Pilar, B1629AHJ Buenos Aires, Argentina
Functional Genomics Facility, University of Colorado School of Medicine, Aurora, CO 80045, USA
Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA
Linda Crnic Institute for Down Syndrome, University of Colorado School of Medicine, Aurora, CO 80045, USA
Author to whom correspondence should be addressed.
Academic Editor: Tarek Abbas
Received: 2 February 2021 / Revised: 23 February 2021 / Accepted: 1 March 2021 / Published: 15 March 2021
Breast cancer has the highest incidence and mortality in women worldwide, and, despite formidable advances in its prevention, detection, and treatment, the development of metastasis foci still represents a significant reduction in patients’ survival and life quality. The Ubiquitin-Proteasome System plays a fundamental role in the maintenance of protein balance, and its dysregulation has been associated with malignant transformation and tumor cells invasive potential. The objective of our work was focused on the identification of ubiquitination-related genes that could represent putative molecular targets for the treatment of breast cancer dissemination. For that purpose, we performed a genetic study and identified and validated HERC1 (HECT and RLD Domain Containing E3 Ubiquitin Protein Ligase Family Member 1) as a regulator of migration and invasion. We confirmed that its depletion reduces tumorigenicity and the appearance of metastasis foci and determined that HERC1 protein expression inversely correlates with breast cancer patients’ overall survival. Altogether, we demonstrate that HERC1 might represent a novel therapeutic target in breast cancer.