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


Authors: Ma, L.; Teruya-Feldstein, J.; Weinberg, R. A.
Article Title: Tumour invasion and metastasis initiated by microRNA-10b in breast cancer
Abstract: 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. ©2007 Nature Publishing Group.
Keywords: controlled study; human tissue; unclassified drug; human cell; cancer growth; nonhuman; animal cell; mouse; animals; mice; animal tissue; gene; gene overexpression; metastasis; peritoneal neoplasms; breast cancer; microrna; gene expression; embryo; lung neoplasms; animal experiment; animal model; protein binding; homeodomain proteins; cell line, tumor; breast neoplasms; transcription factors; cancer invasion; rna; gene expression regulation, neoplastic; cancer cell; neoplasm metastasis; cell migration; cell movement; base sequence; neoplasm invasiveness; homeodomain protein; micrornas; tumor; transcription factor twist; cell invasion; rho gtp-binding proteins; inhibition; twist transcription factor; protein d10; rhoc gene
Journal Title: Nature
Volume: 449
Issue: 7163
ISSN: 0028-0836
Publisher: Nature Publishing Group  
Date Published: 2007-10-11
Start Page: 682
End Page: 688
Language: English
DOI: 10.1038/nature06174
PUBMED: 17898713
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 546" - "Export Date: 17 November 2011" - "CODEN: NATUA" - "Source: Scopus"
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  1. Julie T Feldstein
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