PCDH10 inhibits cell proliferation of multiple myeloma via the negative regulation of the Wnt/β-catenin/BCL-9 signaling pathway

Xu,Yonghui; Yang,Zesong; Yuan,Haiting; Li,Zhen; Li,Ying; Liu,Qiong; Chen,Jianbin

doi:10.3892/or.2015.4056

PCDH10 inhibits cell proliferation of multiple myeloma via the negative regulation of the Wnt/β-catenin/BCL-9 signaling pathway

Authors:
- Yonghui Xu
- Zesong Yang
- Haiting Yuan
- Zhen Li
- Ying Li
- Qiong Liu
- Jianbin Chen
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Affiliations: Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P.R. China, Department of Hematology, The Third Military Medical University, Chongqing, P.R. China, Department of Hematology, Chongqing Three Gorges Central Hospital, Chongqing, P.R. China, Department of Emergency, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P.R. China
Published online on: June 11, 2015 https://doi.org/10.3892/or.2015.4056
Pages: 747-754

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Abstract

The tumor suppressor protocadherin-10 (PCDH10) gene is important in cell proliferation, survival, apoptosis and migration. Inactivation of PCDH10 by promoter methylation is a frequent pathogenetic event in multiple myeloma (MM). The Wnt/β-catenin pathway is known to be involved in the cell growth of various types of cancer, including MM. However, the relationship between PCDH10 and Wnt signaling in MM remains unclear. In this study, we found that PCDH10 deficiency highly enhanced MM cell proliferation, Wnt signaling and the expression of BCL-9, an essential coactivator of Wnt transcriptional activity that is correlated with cell growth, survival and drug resistance. Restoration of PCDH10 suppressed nuclear localization of β-catenin, the activity of LEF/TCF, the expression of BCL-9 and AKT, whereas the expression of GSK3β was increased. The antagonistic effect of PCDH10 was associated with G1‑phase blockage. Collectively, PCDH10 antagonized MM cell proliferation via the downregulation of Wnt/β-catenin/BCL-9 signaling, whereas PCDH10 repressed the expression of AKT to promote the expression of GSK3β and then to restrain the activation of β-catenin. Thus, the results offer a novel preclinical rationale in order to explore PCDH10 as an effective and selective therapeutic strategy to eradicate MM cells.

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