title: Phosphatidylinositol glycan anchor biosynthesis, class X containing complex promotes cancer cell proliferation through suppression of EHD2 and ZIC1, putative tumor suppressors.
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.
authors: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL, USA.
authors: Makoto
authors: M
authors: Nakakido
authors: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL, USA.
authors: Kenji
authors: K
authors: Tamura
authors: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL, USA.
authors: Suyoun
authors: S
authors: Chung
authors: Project for Realization of Personalized Cancer Medicine, Genome Center, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors: Koji
authors: K
authors: Ueda
authors: Project for Realization of Personalized Cancer Medicine, Genome Center, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors: Risa
authors: R
authors: Fujii
authors: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL, USA.
authors: Kazuma
authors: K
authors: Kiyotani
authors: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL, USA.
authors: Yusuke
authors: Y
authors: Nakamura
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D008364:Mannosyltransferases / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; C406446:EHD2 protein, human; C000597745:RCN1 protein, human; C088393:RCN2 protein, human; D014157:Transcription Factors; C492123:ZIC1 protein, human; D008364:Mannosyltransferases; C502828:PIGX protein, human