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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
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