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

Abstract

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.

Cleistanthin A inhibits the invasion and metastasis of human melanoma cells by inhibiting the expression of matrix metallopeptidase‑2 and ‑9

“…Recently, it was reported that the transcription of MT1-MMP was regulated by the Wnt signaling pathway (28,29). It is necessary to determine whether CA inhibits the activation of MMPs via the Wnt signaling pathway through further study.…”

Roles of matrix metalloproteinase-26 in the growth, invasion and angiogenesis of breast cancer

“…There are four main types of proteolytic enzymes taking part in the degradation of ECM, among which MMPs are the largest family with the most complicated functions and high proteolytic activity. MMPs are involved in the metastasis and invasion of cancers by degrading the ECM, regulating cell adherence and promoting angiogenesis (1)(2)(3)(4)(5).…”

“…An increasing number of studies indicate that matrix metalloproteinases (MMPs) contribute to the malignant phenotype, and that the evaluation of MMP expression may be helpful for the assessment of patients' prognosis (1)(2)(3)(4)(5). MMPs are a family of zinc-dependent endopeptidases with multiple functions, including proteolytic activity.…”

Understanding the role of the MYB oncogene in human breast cancer: targets and functions

“…Furthermore, the TGFβ-mediated MYB expression controls the expression of EMT-associated genes and promotes the invasion of ER + breast cancer cells (Cesi et al, 2011, Hugo et al, 2013. Moreover, MYB up-regulates cathepsin D to contribute to cell migration and invasion in human breast cancer cell line MDA-MB-231 (Knopfova et al, 2012). This evidence shows MYB may be involved in breast cancer metastasis.…”

“…MYB promoted breast cancer proliferation (Drabsch et al, 2007), invasion and metastasis (Knopfova et al, 2012, Li et al, 2016. Metastatic breast cancers in the bone (Ogba et al, 2014, Savci-Heijink et al, 2016 and lymph nodes (Harrell et al, 2006, Ogba et al, 2014 expressed ER.…”