Cited by 191MicroRNA in disease regulationHER2/EGFR in Cancer ResearchMechanisms of cancer metastasis

Up-regulation of miR-21 by HER2/neu signaling promotes cell invasion

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Huang, Tzu-Hsuan, Wu, Fangting, Loeb, Gabriel B., Hsu, Ruby, Heidersbach, Amy, Brincat, Allison, Horiuchi, Dai, Lebbink, Robert J. +3 more·2009·Journal of Biological Chemistry

Abstract

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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  • EGFR and HER2/neu signaling positively regulates miR-21 expression in human lung and breast carcinoma cell lines, respectively.

    “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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  1. Guy, C. T., Webster, M. A., Schaller, M., Parsons, T. J., Cardiff, R. D., and Muller, W. J. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 10578 -10582
  2. Taganov, K. D., Boldin, M. P., Chang, K. J., and Baltimore, D. (2006) Proc. Natl. Acad. Sci. U.S.A. 103, 12481-12486
  3. Ventura, A., Meissner, A., Dillon, C. P., McManus, M., Sharp, P. A., Van Parijs, L., Jaenisch, R., and Jacks, T. (2004) Proc. Natl. Acad. Sci. U.S.A. 101, 10380 -10385
  4. Fong, S., Itahana, Y., Sumida, T., Singh, J., Coppe, J. P., Liu, Y., Richards, P. C., Bennington, J. L., Lee, N. M., Debs, R. J., and Desprez, P. Y. (2003) Proc. Natl. Acad. Sci. U.S.A. 100, 13543-13548

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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.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2009-07
Volume
284
Issue
27
Pages
18515-18524
ISSN
0021-9258 (ISSN-L)
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
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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