c-Myb regulates matrix metalloproteinases 1/9, and cathepsin D: implications for matrix-dependent breast cancer cell invasion and metastasis

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Authors

KNOPFOVÁ Lucia BENEŠ Petr PEKARČÍKOVÁ Lucie HERMANOVÁ Markéta MASAŘÍK Michal PERNICOVÁ Zuzana SOUČEK Karel ŠMARDA Jan

Year of publication 2012
Type Article in Periodical
Magazine / Source Molecular Cancer
MU Faculty or unit

Faculty of Science

Citation
Doi http://dx.doi.org/10.1186/1476-4598-11-15
Field Genetics and molecular biology
Keywords c-Myb; Metastasis; Breast cancer; Matrix metalloproteinase; Cathepsin D; Extracellular matrix
Description The aim of this study was to investigate the role of c-Myb in the metastatic spread of breast tumors. We ectopically expressed c-Myb in human MDA-MB-231 and mouse 4T1 mammary cancer cells to find that c-Myb enhanced migration and ability of these cells to invade Matrigel but not the collagen I matrix in vitro. c-Myb strongly increased the expression/activity of cathepsin D and matrix metalloproteinase (MMP) 9 and significantly downregulated MMP1. The gene coding for cathepsin D was found to act as the c-Myb-responsive gene and downstream effector of the migration-promoting function of c-Myb. Finally, we demonstrated that c-Myb delayed the growth of mammary tumors in BALB/c mice and affected the metastatic potential of breast cancer cells in an organ-specific manner. This study identified c-Myb as a matrix-dependent regulator of invasive behavior of breast cancer cells.
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