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

Autor: Sikandar SS; Institute for Stem Cell Biology and Regenerative Medicine, School of Medicine, 265 Campus Drive, Stanford, CA, 94305, USA., Kuo AH; Institute for Stem Cell Biology and Regenerative Medicine, School of Medicine, 265 Campus Drive, Stanford, CA, 94305, USA., Kalisky T; Department of Bioengineering, 318 Campus Drive, Stanford, CA, 94305, USA.; Faculty of Engineering, Bar-Ilan University, Ramat Gan, 52900, Israel., Cai S; Institute for Stem Cell Biology and Regenerative Medicine, School of Medicine, 265 Campus Drive, Stanford, CA, 94305, USA., Zabala M; Institute for Stem Cell Biology and Regenerative Medicine, School of Medicine, 265 Campus Drive, Stanford, CA, 94305, USA., Hsieh RW; Institute for Stem Cell Biology and Regenerative Medicine, School of Medicine, 265 Campus Drive, Stanford, CA, 94305, USA., Lobo NA; Institute for Stem Cell Biology and Regenerative Medicine, School of Medicine, 265 Campus Drive, Stanford, CA, 94305, USA., Scheeren FA; Institute for Stem Cell Biology and Regenerative Medicine, School of Medicine, 265 Campus Drive, Stanford, CA, 94305, USA.; Department of Medical Oncology, Leiden University Medical Center, Leiden, RC, 2300, The Netherlands., Sim S; Institute for Stem Cell Biology and Regenerative Medicine, School of Medicine, 265 Campus Drive, Stanford, CA, 94305, USA., Qian D; Institute for Stem Cell Biology and Regenerative Medicine, School of Medicine, 265 Campus Drive, Stanford, CA, 94305, USA., Dirbas FM; Department of Surgery, Stanford University School of Medicine, Stanford Cancer Institute, 875 Blake Wilbur Drive, Rm CC2235, Stanford, CA, 94305, USA., Somlo G; City of Hope Comprehensive Cancer Center, 1500 East Duarte Road, Duarte, CA, 91010, USA., Quake SR; Department of Bioengineering, 318 Campus Drive, Stanford, CA, 94305, USA., Clarke MF; Institute for Stem Cell Biology and Regenerative Medicine, School of Medicine, 265 Campus Drive, Stanford, CA, 94305, USA. mfclarke@stanford.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2017 Nov 21; Vol. 8 (1), pp. 1669. Date of Electronic Publication: 2017 Nov 21.
DOI: 10.1038/s41467-017-01666-2
Abstrakt: 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.
Databáze: MEDLINE
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