Matrix metalloproteinase-9 (MMP-9) plays an important role in the invasion and metastasis of cancer cells. However, the regulatory mechanism of MMP-9 expression and its biological effects on breast cancer development remain obscure. In the current study, we examined the potential role of annexin A1 (ANXA1) in regulating migration and invasion in breast cancer cell lines. Both ANXA1 mRNA and protein are expressed in the highly invasive, hormone-insensitive human breast cancer cell lines MDA-MB-231 and SKBr3, but not in the hormone-responsive cell lines MCF-7 and T47D. Downregulation of ANXA1 expression with specific small interfering RNAs (ANXA1 siRNA) in MDA-MB-231 cells resulted in decreased cancer cell migration and invasion. Ablation of ANXA1 expression decreases the expression of MMP-9 at both the mRNA and protein levels and also reduces the proteolytic activity of MMP-9 in MDA-MB-231 cells. Moreover, silencing . ANXA1 also decreases the transcriptional activity of MMP-9 by the suppression of nuclear factor kappa-B (NF-κB) activity. Collectively, these results indicate that ANXA1 functions as a positive regulator of MMP-9 expression and invasion of breast cancer cells through specific activation of the NF-κB signaling pathway.
|Number of pages
|Biochemical and biophysical research communications
|Published - 2012 Jun 22
Bibliographical noteFunding Information:
This research was supported by basic science research program (2011-0026360) to S.-W. Jang, and (2012-0004978) to J. Ko through the National Research Foundation of Korea (NRF) funded by the ministry of education, science and technology and Asan Institute for Life Sciences, Seoul, Korea (2012-529).
- Annexin A1
- Breast cancer
- Cell invasion
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology