Breast Cancer Malignant Processes are Regulated by Pax-5 Through the Disruption of FAK Signaling Pathways

Sami Benzina^1,2, Jason Harquail^1,2, Roxann Guerrette^1,2, Pierre O'Brien^1,2, Stéphanie Jean^1,2, Nicolas Crapoulet¹, Gilles A. Robichaud^1,2✉

1. Department of Chemistry and Biochemistry, Université de Moncton, Moncton, NB, Canada E1A 3E9.
2. Atlantic Cancer Research Institute, Moncton, NB, Canada E1C 8X3.

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Citation:
Benzina S, Harquail J, Guerrette R, O'Brien P, Jean S, Crapoulet N, Robichaud GA. Breast Cancer Malignant Processes are Regulated by Pax-5 Through the Disruption of FAK Signaling Pathways. J Cancer 2016; 7(14):2035-2044. doi:10.7150/jca.15200. Available from https://www.jcancer.org/v07p2035.htm

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.

Keywords: FAK, Pax-5, Breast cancer, EMT-MET, NFκB, migration, metastasis.