Phosphatidylinositol glycan anchor biosynthesis, class X containing complex promotes cancer cell proliferation through suppression of EHD2 and ZIC1, putative tumor suppressors

Nakakido,Makoto; Tamura,Kenji; Chung,Suyoun; Ueda,Koji; Fujii,Risa; Kiyotani,Kazuma; Nakamura,Yusuke

doi:10.3892/ijo.2016.3607

Phosphatidylinositol glycan anchor biosynthesis, class X containing complex promotes cancer cell proliferation through suppression of EHD2 and ZIC1, putative tumor suppressors

Authors:
- Makoto Nakakido
- Kenji Tamura
- Suyoun Chung
- Koji Ueda
- Risa Fujii
- Kazuma Kiyotani
- Yusuke Nakamura
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Affiliations: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL, USA, Project for Realization of Personalized Cancer Medicine, Genome Center, Japanese Foundation for Cancer Research, Tokyo, Japan
Published online on: July 6, 2016 https://doi.org/10.3892/ijo.2016.3607
Pages: 868-876
Copyright: © Nakakido et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

We identified phosphatidylinositol glycan anchor biosynthesis, class X (PIGX), which plays a critical role in the biosynthetic pathway of glycosylphosphatidylinositol (GPI)-anchor motif, to be upregulated highly and frequently in breast cancer cells. Knockdown of PIGX as well as reticulocalbin 1 (RCN1) and reticulocalbin 2 (RCN2), which we found to interact with PIGX and was indicated to regulate calcium-dependent activities, significantly suppressed the growth of breast cancer cells. We also identified PIGX to be a core protein in an RCN1/PIGX/RCN2 complex. Microarray analysis revealed that the expression of two putative tumor suppressor genes, Zic family member 1 (ZIC1) and EH-domain containing 2 (EHD2), were upregulated commonly in cells in which PIGX, RCN1, or RCN2 was knocked down, suggesting that this RCN1/PIGX/RCN2 complex could negatively regulate the expression of these two genes and thereby contribute to human breast carcinogenesis. Our results imply that PIGX may be a good candidate molecule for development of novel anticancer drugs for breast cancer.

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