Cited by 2,605MicroRNA in disease regulationMechanisms of cancer metastasisCancer Cells and Metastasis

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

Ma, Li, Teruya-Feldstein, Julie, Weinberg, Robert A.·2007·Nature

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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.

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Authors: Ma, L., Teruya-Feldstein, J., & Weinberg, R. A.
Affiliations: Whitehead Institute for Biomedical Research (US)
Corresponding author: Weinberg, Robert A.
ORCID: Ma, Li
Weinberg, Robert A.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2007-09-26
Volume: 449
Issue: 7163
Pages: 682-688
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature06174
OpenAlex: W2047529648
Cited by: 2,605
References: 49
Citations by year: 2026: 34 · 2025: 36 · 2024: 66 · 2023: 69 · 2022: 75 · 2021: 120 · 2020: 106 · 2019: 123 · 2018: 113 · 2017: 151 · 2016: 160 · 2015: 196 · 2014: 215 · 2013: 226 · 2012: 220
FWCI: 60.84
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Keywords: microRNA-10b, breast cancer, metastasis, tumor invasion, cell migration, Twist transcription factor, HOXD10, RhoC, Hox genes, microRNA target regulation, clinical progression
MeSH terms: rhoC GTP-Binding Protein, Animals, Base Sequence, Breast Neoplasms, Cell Movement, Humans, Lung Neoplasms, Neoplasm Invasiveness, Neoplasm Metastasis, Peritoneal Neoplasms, Transcription Factors, Gene Expression Regulation, Neoplastic, Homeodomain Proteins, rho GTP-Binding Proteins, MicroRNAs, Cell Line, Tumor, Mice, Twist-Related Protein 1

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

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