Functional genome screen for therapeutic targets of osteosarcoma

Umio Yamaguchi, Kazufumi Honda, Reiko Satow, Eisuke Kobayashi, Robert Nakayama, Hitoshi Ichikawa, Ayako Shoji, Miki Shitashige, Mari Masuda, Akira Kawai, Hirokazu Chuman, Yukihide Iwamoto, Setsuo Hirohashi, Tesshi Yamada

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Osteosarcoma (OS) is the most frequent primary malignant bone tumor of children and young adults. Although the introduction of combined neoadjuvant chemotherapy has markedly improved survival, the outcome of OS patients with distant metastasis and/or poor response to chemotherapy is still unsatisfactory. Therefore there is a need to develop new therapeutic agents that suppress OS cell proliferation with higher efficacy. The protein kinases are a family of genes that play critical roles in various signaling pathways. Some cancer cells show addiction to constitutive activation of certain signaling pathways for proliferation and survival. To identify new drug targets for OS, we screened a panel of small interfering RNAs (siRNAs) that target 691 genes encoding human protein kinases and related proteins. We found that different constructs of siRNA specifically targeting polo-like 1 kinase (PLK1) significantly caused mitotic cell cycle arrest and subsequent apoptotic cell death in a variety of OS cell lines. siRNA targeting PLK1 also suppressed the growth of OS xenografts established in immunodeficient mice. Recently, phase I clinical trials of PLK1 chemical inhibitors have been reported. Our results indicate that PLK1 is a promising molecular target for pharmacologic intervention in OS.

Original languageEnglish
Pages (from-to)2268-2274
Number of pages7
JournalCancer science
Volume100
Issue number12
DOIs
Publication statusPublished - 2009 Dec 1
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Yamaguchi, U., Honda, K., Satow, R., Kobayashi, E., Nakayama, R., Ichikawa, H., Shoji, A., Shitashige, M., Masuda, M., Kawai, A., Chuman, H., Iwamoto, Y., Hirohashi, S., & Yamada, T. (2009). Functional genome screen for therapeutic targets of osteosarcoma. Cancer science, 100(12), 2268-2274. https://doi.org/10.1111/j.1349-7006.2009.01310.x