Kana Ishibashi1, Kotaro Ishii1, Goro Sugiyama2, Y U Kamata1, Azusa Suzuki1, Wataru Kumamaru1, Yukiko Ohyama1, Hiroyuki Nakano1, Tamotsu Kiyoshima3, Tomoki Sumida1, Tomohiro Yamada1, Yoshihide Mori1. 1. Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan. 2. Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan gs5603@dent.kyushu-u.ac.jp. 3. Laboratory of Oral Pathology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
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. Copyright
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. Copyright
Authors: Lauren F Watt; Nikita Panicker; Abdul Mannan; Ben Copeland; Richard G S Kahl; Matthew D Dun; Barbara Young; Severine Roselli; Nicole M Verrills Journal: Breast Cancer Res Treat Date: 2017-07-25 Impact factor: 4.872
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