Skip to content
Journal article

miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis

Ma L, Young J, Prabhala H, Pan E, Mestdagh P, Muth D, Teruya-Feldstein J, Reinhardt F, Onder T, Valastyan S, Westermann F, Speleman F, Vandesompele J, Weinberg R ...see all

Nature Cell Biology (2010)

  • 383

    Readers

    Mendeley users who have this article in their library.
  • 716

    Citations

    Citations of this article.
  • N/A

    Views

    ScienceDirect users who have downloaded this article.
Sign in to save reference

Abstract

MicroRNAs (miRNAs) are increasingly implicated in regulating the malignant progression of cancer. Here we show that miR-9, which is upregulated in breast cancer cells, directly targets CDH1, the E-cadherin-encoding messenger RNA, leading to increased cell motility and invasiveness. miR-9-mediated E-cadherin downregulation results in the activation of Β-catenin signalling, which contributes to upregulated expression of the gene encoding vascular endothelial growth factor (VEGF); this leads, in turn, to increased tumour angiogenesis. Overexpression of miR-9 in otherwise non-metastatic breast tumour cells enables these cells to form pulmonary micrometastases in mice. Conversely, inhibiting miR-9 by using a 'miRNA sponge' in highly malignant cells inhibits metastasis formation. Expression of miR-9 is activated by MYC and MYCN, both of which directly bind to the mir-9-3 locus. Significantly, in human cancers, miR-9 levels correlate with MYCN amplification, tumour grade and metastatic status. These findings uncover a regulatory and signalling pathway involving a metastasis-promoting miRNA that is predicted to directly target expression of the key metastasis-suppressing protein E-cadherin. © 2010 Macmillan Publishers Limited. All rights reserved.

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Get full text

Authors

  • Li Ma

  • Jennifer Young

  • Harsha Prabhala

  • Elizabeth Pan

  • Pieter Mestdagh

  • Daniel Muth

Cite this document

Choose a citation style from the tabs below