Pax-5 is a potent regulator of E-cadherin and breast cancer malignant processes

// Sami Benzina 1, 2 , Annie-Pier Beauregard 1, 2 , Roxann Guerrette 1, 2 , Stephanie Jean 1, 2 , Mame Daro Faye 1, 2 , Mark Laflamme 1, 3 , Emmanuel Maicas 1, 2, 4 , Nicolas Crapoulet 2 , Rodney J. Ouellette 1, 2 , Gilles A. Robichaud 1, 2 1 Universite de Moncton, Departement de chimie et biochimie, Moncton, NB, E1A 3E9, Canada 2 Atlantic Cancer Research Institute, Moncton, NB, E1C 8X3, Canada 3 Department of Fisheries and Oceans Canada, Molecular Biology Unit, Moncton, NB, E1C 9B6, Canada 4 Georges-L.-Dumont University Hospital Centre, Pathology Department, Moncton, NB, E1C 2Z3, Canada Correspondence to: Gilles A. Robichaud, email: gilles.robichaud@umoncton.ca Keywords: Pax-5, breast cancer, EMT-MET, E-cadherin, metastasis Received: April 13, 2016      Accepted: December 16, 2016      Published: January 05, 2017 ABSTRACT Pax-5, an essential transcription factor for B lymphocyte development, has been linked with the development and progression of lymphoid cancers and carcinoma. In contrast to B-cell cancer lesions, the specific expression signatures and roles of Pax-5 in breast cancer progression are relatively unknown. In the present study, we set out to profile Pax-5 expression in mammary tissues and elucidate the cellular and molecular roles of Pax-5 in breast cancer processes. Using immunohistology on mammary tissue arrays, Pax-5 was detected in a total of 298/306 (97.6%) samples tested. Interestingly, our studies reveal that Pax-5 inhibits aggressive features and confers anti-proliferative effects in breast carcinoma cells in contrast to its oncogenic properties in B cell cancers. More precisely, Pax-5 suppressed breast cancer cell migration, invasion and tumor spheroid formation while concomitantly promoting cell adhesion properties. We also observed that Pax-5 inhibited and reversed breast cancer epithelial to mesenchymal phenotypic transitioning. Mechanistically, we found that the Pax-5 transcription factor binds and induces gene expression of E-cadherin, a pivotal regulator of epithelialisation. Globally, we demonstrate that Pax-5 is predominant expressed factor in mammary epithelial cells. We also present an important role for Pax-5 in the phenotypic transitioning processes and aggressive features associated with breast cancer malignancy and disease progression.