The epithelial-mesenchymal transition generates cells with properties of stem cells

被引:7230
作者
Mani, Sendurai A. [1 ,3 ]
Guo, Wenjun [1 ]
Liao, Mai-Jing [1 ]
Eaton, Elinor Ng. [1 ]
Ayyanan, Ayyakkannu [4 ]
Zhou, Alicia Y. [1 ,2 ]
Brooks, Mary [1 ]
Reinhard, Ferenc [1 ]
Zhang, Cheng Cheng [1 ]
Shipitsin, Michail [5 ,6 ]
Campbell, Lauren L. [5 ,7 ]
Polyak, Kornelia [5 ,6 ,7 ]
Brisken, Cathrin [4 ]
Yang, Jing [8 ]
Weinberg, Robert A. [1 ,2 ]
机构
[1] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA
[2] MIT, Dept Biol, Cambridge, MA 02139 USA
[3] Univ Texas MD Anderson Canc Ctr, Dept Mol Pathol, Houston, TX 77054 USA
[4] Swiss Inst Expt Canc Res, NCCR Mol Oncol, Ecole Polytech Fed Lausanne, CH-1066 Epalinges, Switzerland
[5] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA
[6] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA
[7] Harvard Univ, Sch Med, Program Biol & Biomed Sci, Boston, MA 02115 USA
[8] Univ Calif San Diego, Sch Med, Dept Pediat & Pharmacol, La Jolla, CA 92093 USA
关键词
D O I
10.1016/j.cell.2008.03.027
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The epithelial-mesenchymal transition (EMT) is a key developmental program that is often activated during cancer invasion and metastasis. We here report that the induction of an EMT in immortalized human mammary epithelial cells (HMLEs) results in the acquisition of mesenchymal traits and in the expression of stem-cell markers. Furthermore, we show that those cells have an increased ability to form mammospheres, a property associated with mammary epithelial stem cells. Independent of this, stem cell-like cells isolated from HMLE cultures form mammospheres and express markers similar to those of HMLEs that have undergone an EMT. Moreover, stem-like cells isolated either from mouse or human mammary glands or mammary carcinomas express EMT markers. Finally, transformed human mammary epithelial cells that have undergone an EMT form mammospheres, soft agar colonies, and tumors more efficiently. These findings illustrate a direct link between the EMT and the gain of epithelial stem cell properties.
引用
收藏
页码:704 / 715
页数:12
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