PIAS1 regulates breast tumorigenesis through selective epigenetic gene silencing

Bin Liu, Samuel Tahk, Kathleen M. Yee, Randy Yang, Yonghui Yang, Ryan Mackie, Cary Hsu, Vasili Chernishof, Neil O'Brien, Yusheng Jin, Guoping Fan, Timothy F Lane, Jianyu Rao, Dennis Slamon, Ke Shuai

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Epigenetic gene silencing by histone modifications and DNA methylation is essential for cancer development. The molecular mechanism that promotes selective epigenetic changes during tumorigenesis is not understood. We report here that the PIAS1 SUMO ligase is involved in the progression of breast tumorigenesis. Elevated PIAS1 expression was observed in breast tumor samples. PIAS1 knockdown in breast cancer cells reduced the subpopulation of tumor-initiating cells, and inhibited breast tumor growth in vivo. PIAS1 acts by delineating histone modifications and DNA methylation to silence the expression of a subset of clinically relevant genes, including breast cancer DNA methylation signature genes such as cyclin D2 and estrogen receptor, and breast tumor suppressor WNT5A. Our studies identify a novel epigenetic mechanism that regulates breast tumorigenesis through selective gene silencing.

Original languageEnglish (US)
Article numbere89464
JournalPloS one
Volume9
Issue number2
DOIs
StatePublished - Feb 24 2014

ASJC Scopus subject areas

  • General

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