P300/CBP-associated factor regulates Y-box binding protein-1 expression and promotes cancer cell growth, cancer invasion and drug resistance

Masaki Shiota, Akira Yokomizo, Yasuhiro Tada, Takeshi Uchiumi, Junichi Inokuchi, Katsunori Tatsugami, Kentaro Kuroiwa, Ken Yamamoto, Narihito Seki, Seiji Naito

研究成果: ジャーナルへの寄稿記事

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Twist1 has been proposed to have oncogenic properties. Although Twist1 was reported to interact with p300/CBP-associated factor (PCAF) and to inhibit the functions of PCAF, it remains unclear how PCAF affects the functions of Twist1, cell growth, invasive ability, and cellular sensitivity to anticancer agents. We found that PCAF, Twist1, and Y-box binding protein-1 (YB-1) expressions were elevated in cisplatin- and doxorubicin-resistant cancer cells. Luciferase reporter assays revealed that PCAF manipulation modulated YB-1 transcription in a Twist1-dependent manner. In addition, PCAF regulated the Twist1 intracellular localization and the Twist1 transcriptional activity through its acetylation function to the Twist1. Suppression of PCAF expression reduced YB-1 expression in human urothelial cancer KK47 cells. As a result, the cell growth and invasive ability of KK47 cells was retarded by PCAF knockdown, and PCAF knockdown rendered KK47 cells sensitive to cisplatin and doxorubicin, but not to 5-fluorouracil. The present data suggest that Twist1 and YB-1 as well as PCAF may be promising molecular therapeutic targets. (Cancer Sci 2010).

元の言語英語
ページ(範囲)1797-1806
ページ数10
ジャーナルCancer Science
101
発行部数8
DOI
出版物ステータス出版済み - 8 1 2010

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All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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