Abstract
Metallopanstimulin-1 (MPS-1) is a multifunctional ribosomal protein RPS27 that contains a zinc finger domain of the C(4) type. MPS-1 has been found to be increased in the sera of a number of different cancers, including head and neck squamous cell carcinoma (HNSCC). However, little is known about the effect of a high-level MPS-1 in regulating cancer cell behavior. In this study, we overexpressed MPS-1 protein in the HNSCC cell line UMSCC-1. We found MPS-1 distributes not only in the cytosol, but also in the nuclei. In addition, MPS-1 is secreted into the culture medium. In vitro and in vivo experiments show that growth of UMSCC-1 cells transfected with MPS-1 is dramatically inhibited. Moreover, we also found that with overexpressing MPS-1, UMSCC-1 cells were arrested on G0/G1 phase, cell proliferation rate was reduced, and tumor angiogenesis was impaired. Further gene array analysis, immunohistochemistry staining and Western blotting reveal that MPS-1 reduces paxillin mRNA and protein levels in UMSCC-1 cells both in vitro and in vivo. Together, these data indicate that when MPS-1 is overexpressed, it has an extraribosomal function as a strong inhibitor of HNSCC tumor cell growth, which may be exerted by reduced paxillin gene expression.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Carcinoma, Squamous Cell / metabolism*
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Carcinoma, Squamous Cell / pathology
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Cell Division
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Cell Line, Tumor / metabolism
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Cell Line, Tumor / transplantation
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Culture Media, Conditioned / pharmacology
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Gene Expression Regulation, Neoplastic / physiology*
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Head and Neck Neoplasms / metabolism*
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Head and Neck Neoplasms / pathology
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Humans
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Male
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Metalloproteins / biosynthesis
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Metalloproteins / genetics
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Metalloproteins / metabolism
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Metalloproteins / physiology*
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Mice
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Mice, Nude
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Neoplasm Proteins / biosynthesis
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism
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Neoplasm Proteins / physiology*
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Neovascularization, Pathologic / metabolism
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Neovascularization, Pathologic / prevention & control
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Nuclear Proteins / biosynthesis
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Nuclear Proteins / physiology*
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Oligonucleotide Array Sequence Analysis
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Paxillin / biosynthesis*
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Paxillin / genetics
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RNA, Messenger / biosynthesis
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RNA, Neoplasm / biosynthesis
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RNA-Binding Proteins / biosynthesis
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RNA-Binding Proteins / genetics
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RNA-Binding Proteins / metabolism
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RNA-Binding Proteins / physiology*
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Recombinant Fusion Proteins / physiology
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Resting Phase, Cell Cycle
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Ribosomal Proteins / biosynthesis
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Ribosomal Proteins / genetics
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Ribosomal Proteins / metabolism
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Ribosomal Proteins / physiology*
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Transfection
Substances
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Culture Media, Conditioned
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Metalloproteins
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Neoplasm Proteins
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Nuclear Proteins
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PXN protein, human
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Paxillin
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RNA, Messenger
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RNA, Neoplasm
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RNA-Binding Proteins
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RPS27 protein, human
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Recombinant Fusion Proteins
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Ribosomal Proteins