title: Kinesin family member 4A: a potential predictor for progression of human oral cancer.
abstract: BACKGROUND
  Kinesin family member 4A (KIF4A), a microtubule-based motor protein, was implicated in regulation of chromosomal structure and kinetochore microtubule dynamics. Considering the functions of KIF4A, we assumed that KIF4A is involved in progression of oral squamous cell carcinomas (OSCCs) via activation of the spindle assembly checkpoint (SAC). However, little is known about the relevance of KIF4A in the behavior of OSCC. We investigated the KIF4A expression status and its functional mechanisms in OSCC.
  
  
  METHODS
  The KIF4A expression levels in seven OSCC-derived cells were analyzed by quantitative reverse transcriptase-polymerase chain reaction and immunoblotting analyses. Using a KIF4A knockdown model, we assessed the expression of (SAC)-related molecules (BUB1, MAD2, CDC20, and cyclin B1), cell-cycle, and cellular proliferation. In addition to in vitro data, the clinical correlation between the KIF4A expression levels in primary OSCCs (n = 106 patients) and the clinicopathologic status by immunohistochemistry (IHC) also were evaluated.
  
  
  RESULTS
  KIF4A mRNA and protein were up-regulated significantly (P < 0.05) in seven OSCC-derived cells compared with human normal oral keratinocytes. In the KIF4A knockdown cells, SAC activation was observed via increased BUB1 expression on the kinetochores, appropriate kinetochore localization of MAD2, down-regulation of CDC20, up-regulation of cyclin B1, and cell-cycle arrested at G2/M phase. The results showed that cellular proliferation of KIF4A knockdown cells decreased significantly (P < 0.05) compared with control cells. IHC showed that KIF4A expression in primary OSCCs was significantly (P < 0.05) greater than in the normal oral counterparts and that KIF4A-positive OSCCs were correlated closely (P < 0.05) with tumoral size.
  
  
  CONCLUSIONS
  Our results proposed for the first time that KIF4A controls cellular proliferation via SAC activation. Therefore, KIF4A might be a key regulator for tumoral progression in OSCCs.
authors.affiliation: Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Minakawa
authors.affiliation: Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, 1-8-1 Inohana, Chiba, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kasamatsu
authors.affiliation: Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, 1-8-1 Inohana, Chiba, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Koike
authors.affiliation: Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, 1-8-1 Inohana, Chiba, Japan.
authors.forename: Morihiro
authors.initials: M
authors.lastname: Higo
authors.affiliation: Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba, Japan.
authors.forename: Dai
authors.initials: D
authors.lastname: Nakashima
authors.affiliation: Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, 1-8-1 Inohana, Chiba, Japan.
authors.forename: Yukinao
authors.initials: Y
authors.lastname: Kouzu
authors.affiliation: Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, 1-8-1 Inohana, Chiba, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Sakamoto
authors.affiliation: Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, 1-8-1 Inohana, Chiba, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Ogawara
authors.affiliation: Department of Medical Oncology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Shiiba
authors.affiliation: Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba, Japan ; Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, 1-8-1 Inohana, Chiba, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Tanzawa
authors.affiliation: Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba, Japan ; Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, 1-8-1 Inohana, Chiba, Japan.
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Uzawa
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016547:Kinesins / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
chemical_list: D009363:Neoplasm Proteins; C484228:KIF4A protein, human; D016547:Kinesins