Regulation of β-Catenin Phosphorylation by PR55β in Adenoid Cystic Carcinoma

Cancer Genomics Proteomics. 2018 Jan-Feb;15(1):53-60. doi: 10.21873/cgp.20064.

Abstract

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. β-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 β-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: PR55β was highly expressed in ACCS-M, suggesting its functional importance. In addition, PR55β expression was associated with tumor grade, with ACCS-M exhibiting higher PR55β levels. More importantly, knockdown of PR55β in ACCS-M cells significantly reduced invasiveness and metastatic ability. Furthermore, dephosphorylation and total levels of β-catenin were dependent on PR55β in ACCS-M. Finally, we confirmed a correlation between PR55β staining intensity and histopathological type in human AdCC tissues.

Conclusion: Our study provides new insight into the interaction between PR55β and β-catenin and suggests that PR55β may be a target for the clinical treatment of AdCC.

Keywords: PP2A; PR55β; adenoid cystic carcinoma; regulatory subunit; salivary gland; β-catenin.

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • Carcinoma, Adenoid Cystic / enzymology*
  • Carcinoma, Adenoid Cystic / metabolism
  • Carcinoma, Adenoid Cystic / pathology
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Humans
  • Mice
  • Neoplasm Grading
  • Nerve Tissue Proteins / metabolism*
  • Phosphorylation
  • Protein Phosphatase 2 / metabolism*
  • Salivary Gland Neoplasms / enzymology*
  • Salivary Gland Neoplasms / metabolism
  • Salivary Gland Neoplasms / pathology
  • beta Catenin / metabolism*

Substances

  • Nerve Tissue Proteins
  • beta Catenin
  • PPP2R2B protein, human
  • Protein Phosphatase 2