title: Overexpression of LIM and SH3 Protein 1 leading to accelerated G2/M phase transition contributes to enhanced tumourigenesis in oral cancer.
abstract: BACKGROUND
  LIM and SH3 protein 1 (LASP-1) is a specific focal adhesion protein involved in several malignant tumors. However, its role in oral squamous cell carcinoma (OSCC) is unknown. The aim of this study was to characterize the role and molecular status/mechanism of LASP-1 in OSCC.
  
  
  METHODS
  We evaluated LASP-1 mRNA and protein expressions in OSCC-derived cell lines and primary OSCCs. Using an shRNA system, we analyzed the effect of LASP-1 on the biology and function of the OSCC cell lines, HSC-3 and Ca9-22. The cells also were subcutaneously injected to evaluate tumor growth in vivo. Data were analyzed by the Fisher's exact test or the Mann-Whitney U test. Bonferroni correction was used for multiple testing.
  
  
  RESULTS
  Significant up-regulation of LASP-1 was detected in OSCC-derived cell lines (n = 7, P<0.007) and primary OSCCs (n = 50, P<0.001) compared to normal controls. LASP-1 knockdown cells significantly inhibited cellular proliferation compared with shMock-transfected cells (P<0.025) by arresting cell-cycle progression at the G2 phase. We observed dramatic reduction in the growth of shLASP-1 OSCC xenografts compared with shMock xenografts in vivo.
  
  
  CONCLUSIONS
  Our results suggested that overexpression of LASP-1 is linked closely to oral tumourigenicity and further provide novel evidence that LASP-1 plays an essential role in tumor cellular growth by mediating G2/M transition.
authors.affiliation: Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Fumie
authors.initials: F
authors.lastname: Shimizu
authors.affiliation: Department of Clinical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Shiiba
authors.affiliation: Division of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chiba, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Ogawara
authors.affiliation: Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Kimura
authors.affiliation: Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Minakawa
authors.affiliation: Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Baba
authors.affiliation: Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yokota
authors.affiliation: Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Dai
authors.initials: D
authors.lastname: Nakashima
authors.affiliation: Division of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chiba, Japan.
authors.forename: Morihiro
authors.initials: M
authors.lastname: Higo
authors.affiliation: Division of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chiba, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kasamatsu
authors.affiliation: Division of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chiba, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Sakamoto
authors.affiliation: Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, Chiba, Japan ; Division of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chiba, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Tanzawa
authors.affiliation: Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, Chiba, Japan ; Division of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chiba, Japan.
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Uzawa
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D063646:Carcinogenesis / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D016195:G2 Phase / Q000235:genetics; D059565:G2 Phase Cell Cycle Checkpoints / Q000235:genetics; D055785:Gene Knockdown Techniques; D006801:Humans; D060588:LIM Domain Proteins / Q000235:genetics* / Q000378:metabolism; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; C096353:LASP1 protein, human; D060588:LIM Domain Proteins; D012333:RNA, Messenger