Phosphatidylinositol glycan anchor biosynthesis, class X containing complex promotes cancer cell proliferation through suppression of EHD2 and ZIC1, putative tumor suppressors.
Phosphatidylinositol glycan anchor biosynthesis, class X containing complex promotes cancer cell proliferation through suppression of EHD2 and ZIC1, putative tumor suppressors.
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DOI：
10.3892/ijo.2016.3607
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发表时间：
2016-09
影响因子：
5.2
通讯作者：
Nakamura Y
中科院分区：
文献类型：
--
作者：
Nakakido M;Tamura K;Chung S;Ueda K;Fujii R;Kiyotani K;Nakamura Y
我们发现，在糖基化磷脂酰肌醇(GPI)-锚定基序的生物合成途径中起关键作用的磷脂酰肌醇-糖锚生物合成X类(PIGX)在乳腺癌细胞中高表达且频繁上调。我们发现与PIGX相互作用的PIGX以及网状钙调素1(RCN1)和网状调素2(RCN2)的敲除显著抑制了乳腺癌细胞的生长。我们还发现PIGX是RCN1/PIGX/RCN2复合体中的核心蛋白。基因芯片分析表明，在PIGX、RCN1或RCN2被敲除的细胞中，两个可能的抑癌基因Zic家族成员1(ZIC1)和EH结构域2(EHD2)的表达普遍上调，表明RCN1/PIGX/RCN2复合体可以负向调节这两个基因的表达，从而促进人类乳腺癌的发生。我们的结果提示PIGX可能是一个很好的候选分子，用于开发新的乳腺癌抗癌药物。
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.