Activation of CDCA1-KNTC2, members of centromere protein complex, involved in pulmonary carcinogenesis.
We found cotransactivation of cell division associated 1 (CDCA1) and kinetochore associated 2 (KNTC2), members of the evolutionarily conserved centromere protein complex, in non-small cell lung carcinomas (NSCLC). Immunohistochemical analysis using lung cancer tissue microarray confirmed high levels of CDCA1 and KNTC2 proteins in the great majority of lung cancers of various histologic types. Their elevated expressions were associated with poorer prognosis of NSCLC patients. Knockdown of either CDCA1 or KNTC2 expression with small interfering RNA significantly suppressed growth of NSCLC cells. Furthermore, inhibition of their binding by a cell-permeable peptide carrying the CDCA1-derived 19-amino-acid peptide (11R-CDCA1(398-416)) that correspond to the binding domain to KNTC2 effectively suppressed growth of NSCLC cells. As our data imply that human CDCA1 and KNTC2 seem to fall in the category of cancer-testis antigens, and that their simultaneous up-regulation is a frequent and important feature of cell growth/survival of lung cancer, selective suppression of CDCA1 or KNTC2 activity and/or inhibition of the CDCA1-KNTC2 complex formation could be a promising therapeutic target for treatment of lung cancers.
Hayama
Satoshi
S
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Daigo
Yataro
Y
Kato
Tatsuya
T
Ishikawa
Nobuhisa
N
Yamabuki
Takumi
T
Miyamoto
Masaki
M
Ito
Tomoo
T
Tsuchiya
Eiju
E
Kondo
Satoshi
S
Nakamura
Yusuke
Y
D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D003598:Cytoskeletal Proteins; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000209:etiology*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D011379:Prognosis; D034741:RNA, Small Interfering / Q000494:pharmacology
D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C120529:NDC80 protein, human; C490197:NUF2 protein, human; D009687:Nuclear Proteins; D034741:RNA, Small Interfering