P300/CBP‐associated factor regulates Y‐box binding protein‐1 expression and promotes cancer cell growth, cancer invasion and drug resistance
P300/CBP‐associated factor regulates Y‐box binding protein‐1 expression and promotes cancer cell growth, cancer invasion and drug resistance
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DOI：
10.1111/j.1349-7006.2010.01598.x
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发表时间：
2010-08
期刊：
影响因子：
5.7
通讯作者：
M. Shiota;A. Yokomizo;Y. Tada;T. Uchiumi;J. Inokuchi;K. Tatsugami;K. Kuroiwa;Ken Yamamoto;N. Seki;S. Naito
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文献类型：
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作者：
M. Shiota;A. Yokomizo;Y. Tada;T. Uchiumi;J. Inokuchi;K. Tatsugami;K. Kuroiwa;Ken Yamamoto;N. Seki;S. Naito
Twist 1被认为具有致癌特性。虽然Twist 1与p300/CBP相关因子（PCAF）相互作用并抑制PCAF的功能，但PCAF如何影响Twist 1的功能、细胞生长、侵袭能力和细胞对抗癌药物的敏感性仍不清楚。我们发现，PCAF，Twist 1和Y-box结合蛋白-1（YB-1）的表达在顺铂和阿霉素耐药的癌细胞中升高。荧光素酶报告基因分析显示，PCAF操作以Twist 1依赖的方式调节YB-1转录。此外，PCAF还通过对Twist 1的乙酰化作用调节Twist 1的细胞内定位和转录活性。抑制PCAF表达可降低人尿路上皮癌KK 47细胞中YB-1的表达。因此，PCAF敲低可延缓KK 47细胞的细胞生长和侵袭能力，PCAF敲低使KK 47细胞对顺铂和阿霉素敏感，但对5-氟尿嘧啶不敏感。目前的数据表明，Twist 1和YB-1以及PCAF可能是有前途的分子治疗靶点。（Cancer Sci 2010）
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)