title: Breast Cancer Malignant Processes are Regulated by Pax-5 Through the Disruption of FAK Signaling Pathways.
abstract: The study of genetic factors regulating breast cancer malignancy is a top priority to mitigate the morbidity and mortality associated with this disease. One of these factors, Pax-5, modulates cancer aggressiveness through the regulation of various components of the epithelial to mesenchymal transitioning (EMT) process. We have previously reported that Pax-5 expression profiles in cancer tissues inversely correlate with those of the Focal Adhesion Kinase (FAK), a potent activator of breast cancer malignancy. In this study, we set out to elucidate the molecular and regulatory relationship between Pax-5 and FAK in breast cancer processes. Interestingly, we found that Pax-5 mediated suppression of breast cancer cell migration is dependent of FAK activity. Our mechanistic examination revealed that Pax-5 inhibits FAK expression and activation. We also demonstrate that Pax-5 is a potent modulator of FAK repressors (p53 and miR-135b) and activator (NFκB) which results in the overall suppression of FAK-mediated signaling cascades. Altogether, our findings bring more insight to the molecular triggers regulating phenotypic transitioning process and signaling cascades leading to breast cancer progression.
authors.affiliation: Department of Chemistry and Biochemistry, Université de Moncton, Moncton, NB, Canada E1A 3E9.; Atlantic Cancer Research Institute, Moncton, NB, Canada E1C 8X3.
authors.forename: Sami
authors.initials: S
authors.lastname: Benzina
authors.affiliation: Department of Chemistry and Biochemistry, Université de Moncton, Moncton, NB, Canada E1A 3E9.; Atlantic Cancer Research Institute, Moncton, NB, Canada E1C 8X3.
authors.forename: Jason
authors.initials: J
authors.lastname: Harquail
authors.affiliation: Department of Chemistry and Biochemistry, Université de Moncton, Moncton, NB, Canada E1A 3E9.; Atlantic Cancer Research Institute, Moncton, NB, Canada E1C 8X3.
authors.forename: Roxann
authors.initials: R
authors.lastname: Guerrette
authors.affiliation: Department of Chemistry and Biochemistry, Université de Moncton, Moncton, NB, Canada E1A 3E9.; Atlantic Cancer Research Institute, Moncton, NB, Canada E1C 8X3.
authors.forename: Pierre
authors.initials: P
authors.lastname: O'Brien
authors.affiliation: Department of Chemistry and Biochemistry, Université de Moncton, Moncton, NB, Canada E1A 3E9.; Atlantic Cancer Research Institute, Moncton, NB, Canada E1C 8X3.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Jean
authors.affiliation: Department of Chemistry and Biochemistry, Université de Moncton, Moncton, NB, Canada E1A 3E9.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Crapoulet
authors.affiliation: Department of Chemistry and Biochemistry, Université de Moncton, Moncton, NB, Canada E1A 3E9.; Atlantic Cancer Research Institute, Moncton, NB, Canada E1C 8X3.
authors.forename: Gilles A
authors.initials: GA
authors.lastname: Robichaud
keywords: Breast cancer; EMT-MET; FAK; NFκB; Pax-5; metastasis.; migration