Up-regulation of miR-21 by HER2/neu signaling promotes cell invasion

Tzu Hsuan Huang, Fangting Wu, Gabriel B. Loeb, Ruby Hsu, Amy Heidersbach, Allison Brincat, Dai Horiuchi, Robert J. Lebbink, Yin Yuan Mo, Andrei Goga, Michael T. McManus*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

171 Scopus citations

Abstract

The Cell surface receptor tyrosine kinase HER2/neu enhances tumor metastasis. Recent studies guggest that deregulated microRNA (miRNA) expression promotes invasion and metastasis of cancer cells; we therefore explored the possibility that HER2/neu signaling induces the expression of specific miRNAs involved in this process. We identified a putative oncogenic miRNA, miR-21, whose expression is correlated with HER2/neu up-regulation and is functionally involved in HER2/neu-induced cell invasion. We show that miR-21 is up-regulated via the MAPK (ERK1/2) pathway upon stimulation of HER2/neu signaling in breast cancer cells, and overexpression of other ERK1/2 activators such as RASV12 or ID-1 is sufficient to induce miR-21 up-regulation in HER2/neu.negative breast cancer cells. Furthermore, the metastasis suppressor protein PDCD4 (programmed cell death 4) is down-regulated by miR-21 in breast cancer cells expressing HER2/neu. Our data reveal a mechanism for HER2/ neu-induced cancer cell invasion via miRNA deregulation. In addition, our results identify miR-21 as a potential therapeutic target for the prevention of breast cancer invasion and metastasis.

Original languageEnglish (US)
Pages (from-to)18515-18524
Number of pages10
JournalJournal of Biological Chemistry
Volume284
Issue number27
DOIs
StatePublished - Jul 3 2009

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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