Retinoic acid induces adhesion and migration in NB4 cells through Pyk2 signaling

Since the introduction of all-. trans-retinoic acid (ATRA) treatment for acute promyelocytic leukemia (APL) there has been increasing concern about extramedullary disease (EMD) progression despite favorable response in the bone marrow. We postulated that ATRA treatment enhances migration and adhesion abilities possibly enabling APL cells to inhabit extramedullary sites. We revealed an increase in adhesion, migration and invasion capabilities of NB4 cells following ATRA treatment. ATRA induced upregulation of Pyk2 mRNA, protein and phosphorylation levels and enhanced Pyk2 interaction with paxillin and vinculin. Pyk2 inhibition resulted in a reduction of NB4 cell adhesion and migration following ATRA treatment. These results indicate that in vitro Pyk2 might function to regulate cell adhesion and motility following ATRA treatment and its upregulated expression may contribute to EMD development in APL patients.