The role of annexin A1 in expression of matrix metalloproteinase-9 and invasion of breast cancer cells.
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.
Department of Medicine, Graduate School, University of Ulsan, Pungnap-2 dong, Songpa-gu, Seoul, South Korea.
Hyereen
H
Kang
Jesang
J
Ko
Sung-Wuk
SW
Jang
D017305:Annexin A1 / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology*; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000235:genetics
D017305:Annexin A1; D016328:NF-kappa B; D034741:RNA, Small Interfering; D004247:DNA; D020780:Matrix Metalloproteinase 9