Kinesin 18A expression: Clinical relevance to colorectal cancer progression

Makoto Nagahara, Naohiro Nishida, Masaaki Iwatsuki, Shinya Ishimaru, Koshi Mimori, Fumiaki Tanaka, Tsuyoshi Nakagawa, Takanobu Sato, Kenichi Sugihara, Dave S.B. Hoon, Masaki Mori

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)2543-2552
Number of pages10
JournalInternational Journal of Cancer
Volume129
Issue number11
DOIs
Publication statusPublished - Dec 1 2011

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Kinesin
Colorectal Neoplasms
Molecular Motor Proteins
Neoplasm Metastasis
Microtubules
Small Interfering RNA
Real-Time Polymerase Chain Reaction
Neoplasms
Colon
Multivariate Analysis
Complementary DNA
Chromosomes
Lymph Nodes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Kinesin 18A expression : Clinical relevance to colorectal cancer progression. / Nagahara, Makoto; Nishida, Naohiro; Iwatsuki, Masaaki; Ishimaru, Shinya; Mimori, Koshi; Tanaka, Fumiaki; Nakagawa, Tsuyoshi; Sato, Takanobu; Sugihara, Kenichi; Hoon, Dave S.B.; Mori, Masaki.

In: International Journal of Cancer, Vol. 129, No. 11, 01.12.2011, p. 2543-2552.

Research output: Contribution to journalArticle

Nagahara, M, Nishida, N, Iwatsuki, M, Ishimaru, S, Mimori, K, Tanaka, F, Nakagawa, T, Sato, T, Sugihara, K, Hoon, DSB & Mori, M 2011, 'Kinesin 18A expression: Clinical relevance to colorectal cancer progression', International Journal of Cancer, vol. 129, no. 11, pp. 2543-2552. https://doi.org/10.1002/ijc.25916
Nagahara, Makoto ; Nishida, Naohiro ; Iwatsuki, Masaaki ; Ishimaru, Shinya ; Mimori, Koshi ; Tanaka, Fumiaki ; Nakagawa, Tsuyoshi ; Sato, Takanobu ; Sugihara, Kenichi ; Hoon, Dave S.B. ; Mori, Masaki. / Kinesin 18A expression : Clinical relevance to colorectal cancer progression. In: International Journal of Cancer. 2011 ; Vol. 129, No. 11. pp. 2543-2552.
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