Importance of RIP140 and LCoR Sub-Cellular Localization for Their Association With Breast Cancer Aggressiveness and Patient Survival

Abstract

New markers are needed to improve diagnosis and to personalize treatments for patients with breast cancer (BC). Receptor-interacting protein of 140 kDa (RIP140) and ligand-dependent corepressor (LCoR), two transcriptional co-regulators of estrogen receptors, strongly interact in BC cells. Although their role in cancer progression has been outlined in the last few years, their function in BC has not been elucidated yet. In this study, we investigated RIP140 and LCoR localization (cytoplasm vs nucleus) in BC samples from a well-characterized cohort of patients (n = 320). RIP140 and LCoR were expressed in more than 80% of tumors, (predominantly in the cytoplasm), and the two markers were highly correlated. Expression of RIP140 and LCoR in the nucleus was negatively correlated with tumor size. Conversely, RIP140 and LCoR cytoplasmic expression strongly correlated with expression of two tumor aggressiveness markers: N-cadherin and CD133 (epithelial mesenchymal transition and cancer stem cell markers, respectively). Finally, high RIP140 nuclear expression was significantly correlated with longer overall survival, whereas high total or cytoplasmic expression of RIP140 was associated with shorter disease-free survival. Our study strongly suggests that the role of RIP140 and LCoR in BC progression could vary according to their prevalent sub-cellular localization, with opposite prognostic values for nuclear and cytoplasmic expression. The involvement in BC progression/invasiveness of cytoplasmic RIP140 could be balanced by the anti-tumor action of nuclear RIP140, thus explaining the previous contradictory findings about its role in BC.