Article

Nature 449, 682-688 (11 October 2007) | doi:10.1038/nature06174; Received 29 June 2007; Accepted 16 August 2007; Published online 26 September 2007

There is an Erratum (11 September 2008) associated with this document.

There is a Brief Communication Arising (23 October 2008) associated with this document.

Tumour invasion and metastasis initiated by microRNA-10b in breast cancer

Li Ma1, Julie Teruya-Feldstein2 & Robert A. Weinberg1

  1. Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA
  2. Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA

Correspondence to: Robert A. Weinberg1 Correspondence and requests for materials should be addressed to R.A.W. (Email: weinberg@wi.mit.edu).

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MicroRNAs have been implicated in regulating diverse cellular pathways. Although there is emerging evidence that some microRNAs can function as oncogenes or tumour suppressors, the role of microRNAs in mediating cancer metastasis remains unexplored. Here we show, using a combination of mouse and human cells, that microRNA-10b (miR-10b) is highly expressed in metastatic breast cancer cells and positively regulates cell migration and invasion. Overexpression of miR-10b in otherwise non-metastatic breast tumours initiates robust invasion and metastasis. Expression of miR-10b is induced by the transcription factor Twist, which binds directly to the putative promoter of mir-10b (MIRN10B). The miR-10b induced by Twist proceeds to inhibit translation of the messenger RNA encoding homeobox D10, resulting in increased expression of a well-characterized pro-metastatic gene, RHOC. Significantly, the level of miR-10b expression in primary breast carcinomas correlates with clinical progression. These findings suggest the workings of an undescribed regulatory pathway, in which a pleiotropic transcription factor induces expression of a specific microRNA, which suppresses its direct target and in turn activates another pro-metastatic gene, leading to tumour cell invasion and metastasis.

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