Abstract
The pentaspan membrane glycoprotein CD133 (also known as prominin-1) has been widely used as a marker for both cancer and normal stem cells. However, the function of CD133 has not been elucidated. Here we describe a cancer stem cell line established from clear cell carcinoma of the ovary (CCC) and show that CD133 interacts with plakoglobin (also known as γ-catenin), a desmosomal linker protein. We further demonstrate that knockdown of CD133 by RNA interference (RNAi) results in the downregulation of desmoglein-2, a desmosomal cadherin, and abrogates cell-cell adhesion and tumorigenicity of CCC stem cells. We speculate that CD133 may be a promising target for cancer chemotherapy.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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AC133 Antigen
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Animals
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Antigens, CD / metabolism*
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Biomarkers, Tumor / metabolism*
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Caco-2 Cells
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Cell Adhesion
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Cell Transformation, Neoplastic / metabolism
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Cell Transformation, Neoplastic / pathology
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Desmoglein 2 / metabolism*
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Glycoproteins / metabolism*
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Humans
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Mice
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Neoplastic Stem Cells / metabolism*
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Neoplastic Stem Cells / pathology
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Peptides / metabolism*
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Protein Binding
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gamma Catenin / metabolism*
Substances
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AC133 Antigen
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Antigens, CD
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Biomarkers, Tumor
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DSG2 protein, human
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Desmoglein 2
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Glycoproteins
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PROM1 protein, human
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Peptides
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Prom1 protein, mouse
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gamma Catenin
Grants and funding
This work was supported by Research Program of Innovative Cell Biology by Innovative Technology (Integrated Systems Analysis of Cellular Oncogenic Signaling Networks), Grants-in-Aid for Scientific Research on Innovative Areas (Integrative Research on Cancer Microenvironment Network) and for Scientific Research (C), Takeda Science Foundation and in part by Global COE Program (Integrative Life Science Based on the Study of Biosignaling Mechanisms), MEXT, Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.