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Up-regulation of miR-21 by HER2/neu Signaling Promotes Cell Invasion
Open accessAbstract
The cell surface receptor tyrosine kinase HER2/neu enhances tumor metastasis. Recent studies suggest 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.
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“As well, epidermal growth factor receptor (EGFR) and HER2/neu signaling positively regulates miR-21 expression in human lung and breast carcinoma cell lines, respectively (Huang et al., 2009; Seike et al., 2009).”
From Modulation of K-Ras-Dependent Lung Tumorigenesis by MicroRNA-21 (2010) · cites this paper as Huang et al., 2009
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Metadata
- Authors
- Huang, T.-H., Wu, F., Loeb, G. B., Hsu, R., Heidersbach, A., Brincat, A., Horiuchi, D., Lebbink, R. J., Mo, Y.-Y., Goga, A., & McManus, M. T.
- Affiliations
- University of California, San Francisco (US)
- SIU Medicine (US)
- Corresponding author
- McManus, Michael T.
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2009-07
- Volume
- 284
- Issue
- 27
- Pages
- 18515-18524
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC2709372
- OpenAlex
- W1998000044
- Cited by
- 191
- References
- 48
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 6 · 2021: 5 · 2020: 11 · 2019: 11 · 2018: 7 · 2017: 6 · 2016: 17 · 2015: 15 · 2014: 21 · 2013: 23 · 2012: 15
- FWCI
- 6.60
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Susan G. Komen for the Cure
- National Institutes of Health (5k08ca104032-05)
- Directorate for Biological Sciences
- University of California, San Francisco
- National Cancer Institute (K08-CA104032, P50CA058207, P50-CA 58207)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Keywords
- miR-21, HER2/neu, cell invasion, breast cancer, MAPK/ERK1/2 signaling, RasV12, Id1, PDCD4, metastasis suppressor, microRNA regulation, therapeutic target
- MeSH terms
- Breast Neoplasms, Female, HeLa Cells, Humans, Neoplasm Invasiveness, Up-Regulation, Gene Expression Regulation, Neoplastic, RNA-Binding Proteins, Receptor, ErbB-2, Erb-b2 Receptor Tyrosine Kinases, Mitogen-Activated Protein Kinase 1, MAP Kinase Signaling System, MicroRNAs, Mitogen-Activated Protein Kinase 3, MAP Kinase Kinase 1, Apoptosis Regulatory Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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