Role of epithelial to mesenchymal transition associated genes in mammary gland regeneration and breast tumorigenesis

Shaheen S. Sikandar, Angera H. Kuo, Tomer Kalisky, Shang Cai, Maider Zabala, Robert W. Hsieh, Neethan A. Lobo, Ferenc A. Scheeren, Sopheak Sim, Dalong Qian, Frederick M. Dirbas, George Somlo, Stephen R. Quake and Michael F. Clarke ()
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Shaheen S. Sikandar: Institute for Stem Cell Biology and Regenerative Medicine, School of Medicine
Angera H. Kuo: Institute for Stem Cell Biology and Regenerative Medicine, School of Medicine
Tomer Kalisky: Department of Bioengineering
Shang Cai: Institute for Stem Cell Biology and Regenerative Medicine, School of Medicine
Maider Zabala: Institute for Stem Cell Biology and Regenerative Medicine, School of Medicine
Robert W. Hsieh: Institute for Stem Cell Biology and Regenerative Medicine, School of Medicine
Neethan A. Lobo: Institute for Stem Cell Biology and Regenerative Medicine, School of Medicine
Ferenc A. Scheeren: Institute for Stem Cell Biology and Regenerative Medicine, School of Medicine
Sopheak Sim: Institute for Stem Cell Biology and Regenerative Medicine, School of Medicine
Dalong Qian: Institute for Stem Cell Biology and Regenerative Medicine, School of Medicine
Frederick M. Dirbas: Stanford University School of Medicine, Stanford Cancer Institute
George Somlo: City of Hope Comprehensive Cancer Center
Stephen R. Quake: Department of Bioengineering
Michael F. Clarke: Institute for Stem Cell Biology and Regenerative Medicine, School of Medicine

Nature Communications, 2017, vol. 8, issue 1, 1-9

Abstract: Abstract Previous studies have proposed that epithelial to mesenchymal transition (EMT) in breast cancer cells regulates metastasis, stem cell properties and chemo-resistance; most studies were based on in vitro culture of cell lines and mouse transgenic cancer models. However, the identity and function of cells expressing EMT-associated genes in normal murine mammary gland homeostasis and human breast cancer still remains under debate. Using in vivo lineage tracing and triple negative breast cancer (TNBC) patient derived xenografts we demonstrate that the repopulating capacity in normal mammary epithelial cells and tumorigenic capacity in TNBC is independent of expression of EMT-associated genes. In breast cancer, while a subset of cells with epithelial and mesenchymal phenotypes have stem cell activity, in many cells that have lost epithelial characteristics with increased expression of mesenchymal genes, have decreased tumor-initiating capacity and plasticity. These findings have implications for the development of effective therapeutic agents targeting tumor-initiating cells.

Date: 2017
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DOI: 10.1038/s41467-017-01666-2

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