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

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 (RC...

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Veröffentlicht in:International journal of oncology 2016-09, Vol.49 (3), p.868-876
Hauptverfasser: Nakakido, Makoto, Tamura, Kenji, Chung, Suyoun, Ueda, Koji, Fujii, Risa, Kiyotani, Kazuma, Nakamura, Yusuke
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Sprache:eng
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Zusammenfassung: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.
ISSN:1019-6439
1791-2423
DOI:10.3892/ijo.2016.3607