Twist promotes tumor cell growth through YB-1 expression

M Shiota, H Izumi, T Onitsuka, N Miyamoto… - Cancer research, 2008 - AACR
M Shiota, H Izumi, T Onitsuka, N Miyamoto, E Kashiwagi, A Kidani, A Yokomizo, S Naito…
Cancer research, 2008AACR
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 …
Abstract
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 G1 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. [Cancer Res 2008;68(1):98–105]
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