Embryonic pathway delivers stem cell traits

“If you take a population of human cancer cells that normally form a tumor very inefficiently and induce an EMT, their tumor-initiating abilities increase by about a hundred-fold, so that it takes about 10,000 cells rather than a million cells to form a tumor,” says Wenjun Guo, co-lead author on the paper and postdoctoral researcher in the Weinberg lab. “This suggests cancer stem cells are using pre-existing normal stem cell machinery to propagate their own self-renewal and therefore their tumor-initiating ability.”

Mani is continuing his research on the EMT/cancer stem cell connection and its role in cancer metastasis at the M. D. Anderson Cancer Center. Researchers in the Weinberg lab will investigate the EMT process with other cell lines. They also will attempt to give final proof in mice that the process creates completely defined stem cells, by taking cells from mouse mammary fat pads, inducing an EMT for some of the cells, returning the resulting cells to the fat pad, and seeing if they can regenerate the mammary gland.

This research was supported by the Breast Cancer Research Foundation, the MIT Ludwig Center for Molecular Oncology and the National Cancer Institute. Mani was supported by a Department of Defense postdoctoral fellowship.

Full citation:

Cell, online publication May 15, Print Edition, Volume 133 (4)
“The epithelial-mesenchymal transition generates cells with properties of stem cells”
Sendurai A. Mani (1,3,9,10), Wenjun Guo (1,9), Mai-Jing Liao (1,9), Elinor Ng Eaton (1), Ayyakkannu Ayyanan (4), Alicia Zhou (1), Mary Brooks (1), Ferenc Reinhard (1), Cheng Cheng Zhang (1), Michail Shipitsin (5,6), Lauren L. Campbell (5,7), Kornelia Polyak (5,6,7), Cathrin Brisken(4), Jing Yang (1,8), Robert A. Weinberg (1,2,).

1. Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142
2. Department of Biology and MIT Ludwig Center for Molecular Oncology, Massachusetts Institute of Technology, Cambridge MA 02139
3. Department of Molecular Pathology, University of Texas M. D. Anderson Cancer Center, 7435 Fannin St, Houston, TX 77054
4. Ecole polytechnique fédérale de Lausanne (EPFL) ISREC - Swiss Institute for Experimental Cancer Research, CH-1066, Epalinges, Switzerland
5. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115
6. Department of Medicine, Harvard Medical School, Boston, MA 02115
7. Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115
8. Department of Pharmacology, University of California, San Diego, School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0636
9. These authors contributed equally to this work