Twist promotes tumor cell growth through YB-1 expression.
YB-1 controls gene expression through both transcriptional and translational mechanisms and is involved in various biological activities such as brain development, chemoresistance, and tumor progression. We have previously shown that YB-1 is overexpressed in cisplatin-resistant cells and is involved in resistance against DNA-damaging agents. Structural analysis of the YB-1 promoter reveals that several E-boxes may participate in the regulation of YB-1 expression. Here, we show that the E-box-binding transcription factor Twist is overexpressed in cisplatin-resistant cells and that YB-1 is a target gene of Twist. Silencing of either Twist or YB-1 expression induces G(1) phase cell cycle arrest of tumor cell growth. Significantly, reexpression of YB-1 led to increase colony formation when Twist expression was down-regulated by small interfering RNA. However, cotransfection of Twist expression plasmid could not increase colony formation when YB-1 expression was down-regulated. Collectively, these data suggest that YB-1 is a major downstream target of Twist. Both YB-1 and Twist expression could induce tumor progression, promoting cell growth and driving oncogenesis in various cancers. Thus, both YB-1 and Twist may represent promising molecular targets for cancer therapy.
Shiota
Masaki
M
Department of Molecular Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Izumi
Hiroto
H
Onitsuka
Takamitsu
T
Miyamoto
Naoya
N
Kashiwagi
Eiji
E
Kidani
Akihiko
A
Yokomizo
Akira
A
Naito
Seiji
S
Kohno
Kimitoshi
K
D000970:Antineoplastic Agents / Q000494:pharmacology; D049109:Cell Proliferation; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000473:pathology*; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D051879:Twist-Related Protein 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051840:Y-Box-Binding Protein 1 / Q000235:genetics / Q000378:metabolism*
D000970:Antineoplastic Agents; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; D051840:Y-Box-Binding Protein 1; D002945:Cisplatin