title: Kinesin 18A expression: clinical relevance to colorectal cancer progression.
abstract: Kif18A, a member of the kinesin superfamily of molecular motor proteins, is a microtubule depolymerase and a key regulator of chromosome congregation. Kif18A's role in cancer progression has not been well defined. Our hypothesis is that Kif18A has a role in the progression of colorectal cancer (CRC). To investigate this expression of Kif18A, mRNA was assessed by quantitative real-time PCR in 113 operative specimens of primary CRC. Kif18A was overexpressed and significantly (p < 0.0001) higher in CRC than in normal colon tissue. Kif18A overexpression in CRC significantly correlated with clinicopathologic factors such as tumor stage (p < 0.0001), lymphatic invasion (p = 0.001), lymph node metastasis (p = 0.01), venous invasion (p = 0.002) and peritoneal dissemination (p = 0.02), suggesting that it has a key role in CRC progression. In multivariate analysis, high Kif18A expression had independent significance for poorer overall survival after resection of CRC (p = 0.037). To demonstrate Kif18A's role in CRC progression, we performed translational and in situ studies. Using in vitro studies on CRC cell lines, we evaluated Kif18A's role in proliferation, migration and invasion. CRC cells transfected with Kif18A cDNA demonstrated significant enhanced migration (p < 0.01) and invasion (p = 0.018) compared to mock-transfected cells. When Kif18A was targeted with specific small interfering RNA, CRC cells had significantly reduced proliferation (p < 0.01), migration (p < 0.01) and invasion (p < 0.05). The in vitro and translational studies demonstrated that Kif18A expression is related to events of metastasis and is a significant factor for CRC progression.
authors.affiliation: Department of Surgery and Molecular Oncology, Medical Institute of Bioregulation, Kyushu University, Beppu, Oita, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Nagahara
authors.forename: Naohiro
authors.initials: N
authors.lastname: Nishida
authors.forename: Masaaki
authors.initials: M
authors.lastname: Iwatsuki
authors.forename: Shinya
authors.initials: S
authors.lastname: Ishimaru
authors.forename: Koshi
authors.initials: K
authors.lastname: Mimori
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Tanaka
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Takanobu
authors.initials: T
authors.lastname: Sato
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sugihara
authors.forename: Dave S B
authors.initials: DS
authors.lastname: Hoon
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D003106:Colon / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D016547:Kinesins / Q000235:genetics* / Q000378:metabolism; D008207:Lymphatic Metastasis; D008297:Male; D009361:Neoplasm Invasiveness; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering; D012007:Rectum / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C502735:KIF18A protein, human; D016547:Kinesins