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Epithelial-Mesenchymal Transition (EMT) in Tumor-Initiating Cells and Its Clinical Implications in Breast Cancer

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Abstract

There is increasing support for the hypothesis that most tumors contain a subpopulation of cells, referred to here as tumor initiating cells (TICs), with the ability to self-renew and to regenerate all the cell types within the tumor. TICs are enriched in breast cancer patients after common treatments, indicating their intrinsic therapeutic resistance. Two independently-derived gene transcription “signatures” of TICs from different studies indicate enrichment of TICs within the recently-identified “claudin-low” intrinsic molecular subtype of breast cancer. These are characterized by high expression of markers associated with epithelial-mesenchymal transition (EMT), suggesting that claudin-low cells may arise from more immature stem or progenitor cells than other breast cancers. EMT is a process by which cells acquire molecular alterations that facilitate dysfunctional cell–cell adhesive interactions and junctions, as well as a more spindle-shaped morphology. These processes may promote cancer cell progression and invasion into the surrounding microenvironment. Induction of EMT in immortalized human mammary epithelial cells results in an increased ability to form mammospheres, and in the expression of stem cell and TIC markers, suggesting that there may be a direct link between the EMT and the gain of TIC properties. Targeting specific molecular pathways—such as Notch, Wnt, and TGFß—associated with development and EMT in the TIC subpopulation, in addition to conventional chemo- and radiation therapies that target the bulk tumor, may ultimately provide a more effective strategy in treating breast cancer. Here, we review recent evidence of the involvement of EMT in breast cancer TICs, focusing on clinical studies.

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Abbreviations

EMT:

Epithelial-mesenchymal transition

TIC:

Tumor-initiating cells

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Acknowledgements

Grant Support: This study was supported in part by the Breast Cancer Research Foundation (JCC), the Helis Foundation (JCC, JMR), the NCI Breast Cancer SPORE P50 CA50183 (JCC, CJC), 1 R01 CA112305-01 from the National Cancer Institute (JCC), P30 CA125123 from the National Institute of Health (JCC, CJC), grant-in-aid from Glaxo Smith Kline (JCC), and US Army Medical Research and Materiel Command DAMD17-01-0132 and W81XWH-04-1-0468 (JCC).

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Authors and Affiliations

  1. Dan L. Duncan Cancer Center Division of Biostatistics, Baylor College of Medicine, Houston, TX, 77030, USA

    Chad J. Creighton

  2. Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, 77030, USA

    Jenny C. Chang & Jeffrey M. Rosen

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  1. Chad J. Creighton
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  2. Jenny C. Chang
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Correspondence to Chad J. Creighton.

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Creighton, C.J., Chang, J.C. & Rosen, J.M. Epithelial-Mesenchymal Transition (EMT) in Tumor-Initiating Cells and Its Clinical Implications in Breast Cancer. J Mammary Gland Biol Neoplasia 15, 253–260 (2010). https://doi.org/10.1007/s10911-010-9173-1

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  • DOI: https://doi.org/10.1007/s10911-010-9173-1

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