TY - JOUR
T1 - Regulation of β-catenin phosphorylation by PR55β in adenoid cystic carcinoma
AU - Ishibashi, Kana
AU - Ishii, Kotaro
AU - Sugiyama, Goro
AU - Kamata, Yu
AU - Suzuki, Azusa
AU - Kumamaru, Wataru
AU - Ohyama, Yukiko
AU - Nakano, Hiroyuki
AU - Kiyoshima, Tamotsu
AU - Sumida, Tomoki
AU - Yamada, Tomohiro
AU - Mori, Yoshihide
N1 - Funding Information:
This work was supported by a Grant-in-Aid (KAKEN No. 17K17262) from the Japan Society for the Promotion of Science (to G. Sugiyama). The Authors appreciate the technical assistance from The Research Support Center, Research Center for Human Disease Modeling, Kyushu University Graduate School of Medical Sciences. The Authors would like to thank Editage (www.editage.jp) for English language editing.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85040190553&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85040190553&partnerID=8YFLogxK
U2 - 10.21873/cgp.20064
DO - 10.21873/cgp.20064
M3 - Article
C2 - 29275362
AN - SCOPUS:85040190553
SN - 1109-6535
VL - 15
SP - 53
EP - 60
JO - Cancer Genomics and Proteomics
JF - Cancer Genomics and Proteomics
IS - 1
ER -
