Regulation of beta-Catenin Phosphorylation by PR55 beta in Adenoid Cystic Carcinoma

Background/Aim: Adenoid cystic carcinoma (AdCC) is a rare cancer of the salivary gland with high risk of recurrence and metastasis. Wnt signalling is critical for determining tumor grade in AdCC, as it regulates invasion and migration. beta-catenin dephosphorylation plays an important role in the Wnt pathway, but its underlying molecular mechanism remains unclear. Materials and Methods: Because the regulatory subunits of protein phosphatase 2A (PP2A) drive Wnt signalling via target molecules, including beta-catenin, we used qRT-PCR and immunoblot analysis to investigate the expression of these subunits in an AdCC cell line (ACCS) and a more aggressive subline (ACCS-M). Results: PR55 beta was highly expressed in ACCS-M, suggesting its functional importance. In addition, PR55 beta expression was associated with tumor grade, with ACCS-M exhibiting higher PR55 beta levels. More importantly, knockdown of PR55 beta in ACCS-M cells significantly reduced invasiveness and metastatic ability. Furthermore, dephosphorylation and total levels of beta-catenin were dependent on PR55 beta in ACCS-M. Finally, we confirmed a correlation between PR55 beta staining intensity and histopathological type in human AdCC tissues. Conclusion: Our study provides new insight into the interaction between PR55 beta and beta-catenin and suggests that PR55 beta may be a target for the clinical treatment of AdCC.