Open AccessP300/CBP‐associated factor regulates Y‐box binding protein‐1 expression and promotes cancer cell growth, cancer invasion and drug resistance
Author(s) -
Shiota Masaki,
Yokomizo Akira,
Tada Yasuhiro,
Uchiumi Takeshi,
Inokuchi Junichi,
Tatsugami Katsunori,
Kuroiwa Kentaro,
Yamamoto Ken,
Seki Narihito,
Naito Seiji
Publication year - 2010
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2010.01598.x
Subject(s) - pcaf , gene knockdown , cancer research , cancer cell , transcription factor , cisplatin , biology , cell growth , cancer , cell culture , biochemistry , genetics , chemotherapy , gene
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)