title: Overexpression of nucleostemin contributes to an advanced malignant phenotype and a poor prognosis in oral squamous cell carcinoma.
abstract: BACKGROUND
  Nucleostemin (NS) is essential for the maintenance of stem cell properties, the functions of which remain poorly understood in cancer cells. The purpose of this study was to explore the impact of NS on malignancy and its clinical significance in oral squamous cell carcinoma (OSCC) patients.
  
  
  METHODS
  We investigated the effects of NS on the proliferation and invasion of OSCC using NS-overexpressing or -knockdown OSCC cells. We assessed the activation of the STAT3 (signal transducer and activator of transcription 3) signalling pathway and the downstream targets in the cells with different expression levels of NS. An immunohistochemical analysis of NS was also performed in 54 OSCC patients who were treated with preoperative chemoradiotherapy and surgery.
  
  
  RESULTS
  The overexpression of NS significantly enhanced the proliferation and invasive potential of OSCC cells. On the other hand, downregulation of NS suppressed the invasiveness of the cells. The alterations of these malignant phenotypes were associated with the activation of STAT3 signalling and its downstream targets. An immunohistochemical analysis demonstrated that a high NS tumour expression level significantly correlated with an advanced T-stage and N-stage. Furthermore, a Cox regression analysis revealed that the NS status (hazard ratio, 9.09; P=0.002) was a significant progression factor for OSCC patients.
  
  
  CONCLUSIONS
  Our results suggest that targeting NS may provide a promising treatment for highly malignant OSCC.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Kumamoto University Graduate School of Life Sciences, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Yoshida
authors.affiliation: Department of Oral and Maxillofacial Surgery, Kumamoto University Graduate School of Life Sciences, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nakayama
authors.affiliation: Department of Oral and Maxillofacial Surgery, Kumamoto University Graduate School of Life Sciences, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Nagata
authors.affiliation: Department of Oral and Maxillofacial Surgery, Kumamoto University Graduate School of Life Sciences, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Hirosue
authors.affiliation: Department of Oral and Maxillofacial Surgery, Kumamoto University Graduate School of Life Sciences, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Oral and Maxillofacial Surgery, Kumamoto University Graduate School of Life Sciences, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kawahara
authors.affiliation: Department of Oral and Maxillofacial Surgery, Kumamoto University Graduate School of Life Sciences, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Nakagawa
authors.affiliation: Department of Oral and Maxillofacial Surgery, Kumamoto University Graduate School of Life Sciences, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuoka
authors.affiliation: Department of Oral and Maxillofacial Surgery, Kumamoto University Graduate School of Life Sciences, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Sakata
authors.affiliation: Department of Oral and Maxillofacial Surgery, Kumamoto University Graduate School of Life Sciences, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Arita
authors.affiliation: Department of Oral and Maxillofacial Surgery, Kumamoto University Graduate School of Life Sciences, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Hiraki
authors.affiliation: Department of Oral and Maxillofacial Surgery, Kumamoto University Graduate School of Life Sciences, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Shinohara
authors.affiliation: Department of Pathology and Experimental Medicine, Kumamoto University Graduate School of Life Sciences, Honjo 1-1-1, Chuo-ku, Kumamoto 860-8556, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ito
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation / Q000502:physiology; D019204:GTP-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D010641:Phenotype; D011379:Prognosis; D015398:Signal Transduction; D000077195:Squamous Cell Carcinoma of Head and Neck; D014162:Transfection
chemical_list: D014408:Biomarkers, Tumor; C469949:GNL3 protein, human; D009687:Nuclear Proteins; D019204:GTP-Binding Proteins