Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2013 Nov 22;2(4):264-82.
doi: 10.3390/jcm2040264.

The Roles of Epithelial-to-Mesenchymal Transition (EMT) and Mesenchymal-to-Epithelial Transition (MET) in Breast Cancer Bone Metastasis: Potential Targets for Prevention and Treatment

Binnaz Demirkan  1
Affiliations
Review

The Roles of Epithelial-to-Mesenchymal Transition (EMT) and Mesenchymal-to-Epithelial Transition (MET) in Breast Cancer Bone Metastasis: Potential Targets for Prevention and Treatment

Binnaz Demirkan. J Clin Med. .

Abstract

Many studies have revealed molecular connections between breast and bone. Genes, important in the control of bone remodeling, such as receptor activator of nuclear kappa (RANK), receptor activator of nuclear kappa ligand (RANKL), vitamin D, bone sialoprotein (BSP), osteopontin (OPN), and calcitonin, are expressed in breast cancer and lactating breast. Epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) effectors play critical roles during embryonic development, postnatal growth, and epithelial homeostasis, but also are involved in a number of pathological conditions, including wound repair, fibrosis, inflammation, as well as cancer progression and bone metastasis. Transforming growth factor β (TGFβ), insulin-like growth factor I & II (IGF I & II), platelet-derived growth factor (PDGF), parathyroid hormone-related protein (PTH(rP)), vascular endothelial growth factor (VEGF), epithelial growth factors II/I (ErbB/EGF), interleukin 6 (IL-6), IL-8, IL-11, IL-1, integrin αvβ3, matrix metalloproteinases (MMPs), catepsin K, hypoxia, notch, Wnt, bone morphogenetic proteins (BMP), and hedgehog signaling pathways are important EMT and MET effectors identified in the bone microenviroment facilitating bone metastasis formation. Recently, Runx2, an essential transcription factor in the regulation of mesenchymal cell differentiation into the osteoblast lineage and proper bone development, is also well-recognized for its expression in breast cancer cells promoting osteolytic bone metastasis. Understanding the precise mechanisms of EMT and MET in the pathogenesis of breast cancer bone metastasis can inform the direction of therapeutic intervention and possibly prevention.

Keywords: breast cancer bone metastasis; epithelial-to-mesenchymal transition (EMT); mesenchymal-to-epithelial transition (MET); prevention; treatment.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Signaling pathways and markers of epithelial to mesenchymal transition (EMT).
Figure 2
Figure 2
Mesenchymal to epithelial transition (MET).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Buijs J.T., van der Pluijm G. Osteotropic cancers: From primary tumor to bone. Cancer Lett. 2009;273:177–193. doi: 10.1016/j.canlet.2008.05.044. - DOI - PubMed
    1. Sporn M.B. The war on cancer. Lancet. 1996;347:1377–1381. doi: 10.1016/S0140-6736(96)91015-6. - DOI - PubMed
    1. Jemal A., Bray F., Center M.M., Ferlay J., Ward E., Forman D. Global cancer statistics. CA Cancer J. Clin. 2011;61:69–90. doi: 10.3322/caac.20107. - DOI - PubMed
    1. Sainsbury R. The development of endocrine therapy for women with breast cancer. Cancer Treat. Rev. 2013;39:507–517. doi: 10.1016/j.ctrv.2012.07.006. - DOI - PubMed
    1. Rao R.D., Cobleigh M.A. Adjuvant endocrine therapy for breast cancer. Oncology (Williston Park) 2012;26:541–547. - PubMed

LinkOut - more resources