ZIP: A novel transcription repressor, represses EGFR oncogene and suppresses breast carcinogenesis

Ruifang Li, Hua Zhang, Wenhua Yu, Yupeng Chen, Bin Gui, Jing Liang, Yan Wang, Luyang Sun, Xiaohan Yang, Yu Zhang, Lei Shi, Yanyan Li, Yongfeng Shang

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Despite the importance of epidermal growth factor receptor (EGFR) in animal development and malignant transformation, surprisingly little is known about the regulation of its expression. Here, we report a novel zinc finger and G-patch domain-containing protein, ZIP. We demonstrated that ZIP acts as a transcription repressor through the recruitment of the nucleosome remodelling and deacetylase complex. Transcriptional target analysis revealed that ZIP regulates several cellular signalling pathways including EGFR pathways that are critically involved in cell proliferation, survival, and migration. We showed that ZIP inhibits cell proliferation and suppresses breast carcinogenesis, and that ZIP depletion leads to a drastic tumour growth in vivo. We found that ZIP is downregulated in breast carcinomas and that its level of expression is negatively correlated with that of EGFR. Our data indicate that ZIP is a novel transcription repressor and a potential tumour suppressor. These findings may shed new light on the EGFR-related breast carcinogenesis and might offer a potential new target for breast cancer therapy.

Original languageEnglish (US)
Pages (from-to)2763-2776
Number of pages14
JournalEMBO Journal
Volume28
Issue number18
DOIs
StatePublished - Sep 16 2009

Keywords

  • Breast cancer
  • EGFR
  • Gene regulation
  • Transcription repressor

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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  • Cite this

    Li, R., Zhang, H., Yu, W., Chen, Y., Gui, B., Liang, J., Wang, Y., Sun, L., Yang, X., Zhang, Y., Shi, L., Li, Y., & Shang, Y. (2009). ZIP: A novel transcription repressor, represses EGFR oncogene and suppresses breast carcinogenesis. EMBO Journal, 28(18), 2763-2776. https://doi.org/10.1038/emboj.2009.211