Therapeutic potential of targeting cell division cycle associated 5 for oral squamous cell carcinoma.
Molecularly targeted drugs are used in the treatment of a variety of malignant tumors, but this approach to developing novel therapies for oral squamous cell carcinoma (OSCC) has lagged behind the progress seen for other cancers. We have attempted to find appropriate molecular targets for OSCC and identified cell division cycle associated 5 (CDCA5) as a cancer-related gene which was overexpressed in all the human OSCC cells tested by microarray analysis. In this study, we investigated the expression and function of CDCA5 in OSCC. First, we confirmed that CDCA5 was overexpressed in 4 human OSCC cell lines by quantitative RT-PCR and Western blotting. We then tested the effect of synthetic small interfering RNAs specific for CDCA5 on the growth and invasion of human OSCC cells. Knockdown of CDCA5 markedly inhibited the growth of OSCC cells in vitro and in vivo. We also examined the expression of CDCA5 protein in 80 cases of OSCC immunohistochemically and found a significant association between CDCA5 expression levels and overall survival. These results suggest that CDCA5 functions as a critical gene supporting OSCC progression and that targeting CDCA5 may be a useful therapeutic strategy for OSCC.
Department of Oral and Maxillofacial Surgery, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan.
Norihiko
N
Tokuzen
Department of Oral and Maxillofacial Surgery, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan.
Koh-ichi
K
Nakashiro
Department of Oral and Maxillofacial Surgery, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan.
Hiroshi
H
Tanaka
Department of Oral and Maxillofacial Surgery, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan.
Kazuki
K
Iwamoto
Department of Oral and Maxillofacial Surgery, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime, Japan.
Hiroyuki
H
Hamakawa
D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis / Q000235:genetics*; D000369:Aged, 80 and over; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics* / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
D048868:Adaptor Proteins, Signal Transducing; C500695:CDCA5 protein, human; D018797:Cell Cycle Proteins; D034741:RNA, Small Interfering
cell cycle; cell division cycle associated 5 (CDCA5); molecular targeted therapy; oral squamous cell carcinoma (OSCC); prognosis