Extraribosomal function of metallopanstimulin-1: reducing paxillin in head and neck squamous cell carcinoma and inhibiting tumor growth.
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.
Dai
Yuemeng
Y
Department of Otolaryngology-Head and Neck Surgery, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
Pierson
Spencer E
SE
Dudney
W Cross
WC
Stack
Brendan C
BC
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division; D045744:Cell Line, Tumor / Q000378:metabolism / Q000637:transplantation; D017077:Culture Media, Conditioned / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008667:Metalloproteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000517:prevention & control; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D051419:Paxillin / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D016601:RNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D016192:Resting Phase, Cell Cycle; D012269:Ribosomal Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014162:Transfection
D017077:Culture Media, Conditioned; D008667:Metalloproteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C496061:PXN protein, human; D051419:Paxillin; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016601:RNA-Binding Proteins; C083686:RPS27 protein, human; D011993:Recombinant Fusion Proteins; D012269:Ribosomal Proteins