J Cancer 2016; 7(14):2035-2044. doi:10.7150/jca.15200
Breast Cancer Malignant Processes are Regulated by Pax-5 Through the Disruption of FAK Signaling Pathways
1. Department of Chemistry and Biochemistry, Université de Moncton, Moncton, NB, Canada E1A 3E9.
2. Atlantic Cancer Research Institute, Moncton, NB, Canada E1C 8X3.
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 http://www.jcancer.org/v07p2035.htm
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.