P300/CBP-associated factor regulates Y-box binding protein-1 expression and promotes cancer cell growth, cancer invasion and drug resistance.
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.
Shiota
Masaki
M
Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Yokomizo
Akira
A
Tada
Yasuhiro
Y
Uchiumi
Takeshi
T
Inokuchi
Junichi
J
Tatsugami
Katsunori
K
Kuroiwa
Kentaro
K
Yamamoto
Ken
K
Seki
Narihito
N
Naito
Seiji
S
D000107:Acetylation; D001483:Base Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002945:Cisplatin / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics*; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D050687:E2F1 Transcription Factor / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000473:pathology*; D009687:Nuclear Proteins / Q000235:genetics* / Q000502:physiology; D014158:Transcription, Genetic; D051879:Twist-Related Protein 1 / Q000502:physiology; D051840:Y-Box-Binding Protein 1; D050880:p300-CBP Transcription Factors / Q000502:physiology*; D000099224:p300-CBP-Associated Factor
D002945:Cisplatin; D004268:DNA-Binding Proteins; D004317:Doxorubicin; D050687:E2F1 Transcription Factor; D009687:Nuclear Proteins; D051879:Twist-Related Protein 1; D051840:Y-Box-Binding Protein 1; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C493753:E2F1 protein, human; C103173:TWIST1 protein, human; C070856:YBX1 protein, human