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

Molecular Cancer

Research

Lucie Pekarčíková¹  Jan Šmarda¹  Lucia Knopfová²  Petr Beneš²  Michal Masařík³  Markéta Hermanová⁴  Zuzana Pernicová⁵  Karel Souček⁵ 

[1] Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic;Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic;International Clinical Research Center, CBCE, St. Anne's University Hospital, Brno, Czech Republic;Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Brno, Czech Republic;First Department of Pathological Anatomy, St. Anne's University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic;International Clinical Research Center, CBCE, St. Anne's University Hospital, Brno, Czech Republic;Department of Cytokinetics, Academy of Sciences of the Czech Republic, Institute of Biophysics, Brno, Czech Republic;

关键词: c-Myb;    Metastasis;    Breast cancer;    Matrix metalloproteinase;    Cathepsin D;    Extracellular matrix;   

DOI  :  10.1186/1476-4598-11-15

 received in 2011-10-21, accepted in 2012-03-23,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundThe c-Myb transcription factor is essential for the maintenance of stem-progenitor cells in bone marrow, colon epithelia, and neurogenic niches. c-Myb malfunction contributes to several types of malignancies including breast cancer. However, the function of c-Myb in the metastatic spread of breast tumors remains unexplored. In this study, we report a novel role of c-Myb in the control of specific proteases that regulate the matrix-dependent invasion of breast cancer cells.ResultsEctopically expressed c-Myb enhanced migration and ability of human MDA-MB-231 and mouse 4T1 mammary cancer 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 suggested 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.ConclusionsThis study identified c-Myb as a matrix-dependent regulator of invasive behavior of breast cancer cells.

【 授权许可】

Unknown   
© Knopfová et al; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.