Oncotarget

Research Papers:

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

Sami Benzina, Annie-Pier Beauregard, Roxann Guerrette, Stéphanie Jean, Mame Daro Faye, Mark Laflamme, Emmanuel Maïcas, Nicolas Crapoulet, Rodney J. Ouellette and Gilles A. Robichaud _

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Oncotarget. 2017; 8:12052-12066. https://doi.org/10.18632/oncotarget.14511

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Abstract

Sami Benzina1,2, Annie-Pier Beauregard1,2, Roxann Guerrette1,2, Stéphanie Jean1,2, Mame Daro Faye1,2, Mark Laflamme1,3, Emmanuel Maïcas1,2,4, Nicolas Crapoulet2, Rodney J. Ouellette1,2, Gilles A. Robichaud1,2

1Université de Moncton, Département de chimie et biochimie, Moncton, NB, E1A 3E9, Canada

2Atlantic Cancer Research Institute, Moncton, NB, E1C 8X3, Canada

3Department of Fisheries and Oceans Canada, Molecular Biology Unit, Moncton, NB, E1C 9B6, Canada

4Georges-L.-Dumont University Hospital Centre, Pathology Department, Moncton, NB, E1C 2Z3, Canada

Correspondence to:

Gilles A. Robichaud, email: [email protected]

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.


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