Bruton's agammaglobulinemia tyrosine kinase (Btk) regulates TPA-induced breast cancer cell invasion via PLC gamma 2/PKC beta/NF-kappa B/AP-1-dependent matrix metalloproteinase-9 activation
- Authors
- Kim, Jeong-Mi; Park, Jinny; Noh, Eun-Mi; Song, Hyun-Kyung; Kang, Sang Yull; Jung, Sung Hoo; Kim, Jong-Suk; Park, Byung-Hyun; Lee, Young-Rae; Youn, Hyun Jo
- Issue Date
- May-2021
- Publisher
- SPANDIDOS PUBL LTD
- Keywords
- Bruton& apos; s agammaglobulinemia tyrosine kinase; matrix metalloproteinase-9; protein kinase C; MCF-7 cells; neoplasm invasiveness
- Citation
- ONCOLOGY REPORTS, v.45, no.5
- Journal Title
- ONCOLOGY REPORTS
- Volume
- 45
- Number
- 5
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/80618
- DOI
- 10.3892/or.2021.8007
- ISSN
- 1021-335X
- Abstract
- Bruton's agammaglobulinemia tyrosine kinase (BTK) is an important cytoplasmic tyrosine kinase involved in B-lymphocyte development, differentiation, and signaling. Activated protein kinase C (PKC), in turn, induces the activation of mitogen-activated protein kinase (MAPK) signaling, which promotes cell proliferation, viability, apoptosis, and metastasis. This effect is associated with nuclear factor-kappa B (NF-kappa B) activation, suggesting an anti-metastatic effect of BTK inhibitors on MCF-7 cells that leads to the downregulation of matrix metalloproteinase (MMP)-9 expression. However, the effect of BTK on breast cancer metastasis is unknown. In this study, the anti-metastatic activity of BTK inhibitors was examined in MCF-7 cells focusing on MMP-9 expression in 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated MCF-7 cells. The expression and activity of MMP-9 in MCF-7 cells were investigated using quantitative polymerase chain reaction analysis, western blotting, and zymography. Cell invasion and migration were investigated using the Matrigel invasion and cell migration assays. BTK inhibitors [ibrutinib (10 mu M), CNX-774 (10 mu M)] significantly attenuated TPA-induced cell invasion and migration in MCF-7 cells and inhibited the activation of the phospholipase C gamma 2/PKC beta signaling pathways. In addition, small interfering RNA specific for BTK suppressed MMP-9 expression and cell metastasis. Collectively, results of the present study indicated that BTK suppressed TPA-induced MMP-9 expression and cell invasion/migration by activating the MAPK or I kappa B kinase/NF-kappa B/activator protein-1 pathway. The results clarify the mechanism of action of BTK in cancer cell metastasis by regulating MMP-9 expression in MCF-7 cells.
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