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Cancers 2013, 5(4), 1545-1565; doi:10.3390/cancers5041545

Interplay of Stem Cell Characteristics, EMT, and Microtentacles in Circulating Breast Tumor Cells

1
Program in Molecular Medicine, University of Maryland School of Medicine, 655 W. Baltimore St., Bressler Bldg., Rm 10-20, Baltimore, MD 21201, USA
2
Marlene and Stewart Greenebaum National Cancer Institute Cancer Center, University of Maryland School of Medicine, 655 W. Baltimore St., Bressler Bldg., Rm 10-29, Baltimore, MD 21201, USA
3
Department of Physiology, University of Maryland School of Medicine, 655 W. Baltimore St., Bressler Bldg., Rm 10-29, Baltimore, MD 21201, USA
*
Author to whom correspondence should be addressed.
Received: 2 September 2013 / Revised: 8 October 2013 / Accepted: 4 November 2013 / Published: 14 November 2013
(This article belongs to the Special Issue Circulating Tumor Cells in Cancers)
View Full-Text   |   Download PDF [570 KB, uploaded 14 November 2013]   |  

Abstract

Metastasis, not the primary tumor, is responsible for the majority of breast cancer-related deaths. Emerging evidence indicates that breast cancer stem cells (CSCs) and the epithelial-to-mesenchymal transition (EMT) cooperate to produce circulating tumor cells (CTCs) that are highly competent for metastasis. CTCs with both CSC and EMT characteristics have recently been identified in the bloodstream of patients with metastatic disease. Breast CSCs have elevated tumorigenicity required for metastatic outgrowth, while EMT may promote CSC character and endows breast cancer cells with enhanced invasive and migratory potential. Both CSCs and EMT are associated with a more flexible cytoskeleton and with anoikis-resistance, which help breast carcinoma cells survive in circulation. Suspended breast carcinoma cells produce tubulin-based extensions of the plasma membrane, termed microtentacles (McTNs), which aid in reattachment. CSC and EMT-associated upregulation of intermediate filament vimentin and increased detyrosination of α-tubulin promote the formation of McTNs. The combined advantages of CSCs and EMT and their associated cytoskeletal alterations increase metastatic efficiency, but understanding the biology of these CTCs also presents new therapeutic targets to reduce metastasis. View Full-Text
Keywords: circulating tumor cells; breast cancer; cancer stem cells; EMT; microtentacles; detyrosinated tubulin circulating tumor cells; breast cancer; cancer stem cells; EMT; microtentacles; detyrosinated tubulin
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Charpentier, M.; Martin, S. Interplay of Stem Cell Characteristics, EMT, and Microtentacles in Circulating Breast Tumor Cells. Cancers 2013, 5, 1545-1565.

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