c-Myb regulates MMP1, MMP9 and cathepsin D: Implications for the matrix-dependent breast cancer cell invasion and metastasis
|Fakulta / Pracoviště MU
|Ectopically expressed c-Myb enhanced motility 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 expression/activity of cathepsin D and matrix metalloproteinase (MMP) 9 and significantly down-regulated MMP1. The gene coding for cathepsin D was identified as direct c-Myb-target gene and downstream effector of the c-Myb migration-promoting function. Finally, we demonstrated that c-Myb delayed growth of mammary tumors in BALB/c mice and affected metastatic potential of breast cancer cells in an organ-specific manner. This study demonstrates potential role of a stromal context for the c-Myb function in control of breast cancer invasion and metastasis.