Twist promotes tumor cell growth through YB-1 expression

Masaki Shiota, Hiroto Izumi, Takamitsu Onitsuka, Naoya Miyamoto, Eiji Kashiwagi, Akihiko Kidani, Akira Yokomizo, Seiji Naito, Kimitoshi Kohno

Research output: Contribution to journalArticlepeer-review

125 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)98-105
Number of pages8
JournalCancer Research
Volume68
Issue number1
DOIs
Publication statusPublished - Jan 1 2008

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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