Transposon mutagenesis identifies genes that cooperate with mutant Pten in breast cancer progression

Roberto Rangel, Song Choon Lee, Kenneth Hon Kim Ban, Liliana Guzman-Rojas, Michael B. Mann, Justin Y. Newberg, Takahiro Kodama, Leslie A. McNoe, Luxmanan Selvanesan, Jerrold M. Ward, Alistair G. Rust, Kuan Yew Chin, Michael A. Black, Nancy A. Jenkins, Neal G. Copeland

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Triple-negative breast cancer (TNBC) has the worst prognosis of any breast cancer subtype. To better understand the genetic forces driving TNBC, we performed a transposon mutagenesis screen in a phosphatase and tensin homolog (Pten) mutant mice and identified 12 candidate trunk drivers and a much larger number of progression genes. Validation studies identified eight TNBC tumor suppressor genes, including the GATA-like transcriptional repressor TRPS1. Down-regulation of TRPS1 in TNBC cells promoted epithelial-to-mesenchymal transition (EMT) by deregulating multiple EMT pathway genes, in addition to increasing the expression of SERPINE1 and SERPINB2 and the subsequent migration, invasion, and metastasis of tumor cells. Transposon mutagenesis has thus provided a better understanding of the genetic forces driving TNBC and discovered genes with potential clinical importance in TNBC.

Original languageEnglish (US)
Pages (from-to)E7749-E7758
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number48
DOIs
StatePublished - Nov 29 2016

Keywords

  • Breast cancer
  • Metastasis
  • Sleeping Beauty
  • TRPS1
  • Tumor suppressors

ASJC Scopus subject areas

  • General

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