TY - JOUR
T1 - Downregulation of miRNA-200c Links Breast Cancer Stem Cells with Normal Stem Cells
AU - Shimono, Yohei
AU - Zabala, Maider
AU - Cho, Robert W.
AU - Lobo, Neethan
AU - Dalerba, Piero
AU - Qian, Dalong
AU - Diehn, Maximilian
AU - Liu, Huiping
AU - Panula, Sarita P.
AU - Chiao, Eric
AU - Dirbas, Frederick M.
AU - Somlo, George
AU - Pera, Renee A.Reijo
AU - Lao, Kaiqin
AU - Clarke, Michael F.
N1 - Funding Information:
We thank Andy Fire for helpful discussions and advice. We thank Jessica S. Lam for technical assistance. This work was supported by the California Breast Cancer Research Program of the University of California #12FB-0053 to Y.S., by the Fundacion Alfonso Martin Escudero and the Fulbright to M.Z., and by the grants from the NIH (NIH CA100225, CA104987, CA126524, CA139490), the Breast Cancer Research Foundation, the Morton Family Foundation, and the Ludwig Foundation to M.F.C. Also, M.F.C. is a consultant for Oncomed Pharmaceuticals, which is developing therapeutics against cancer stem cells.
PY - 2009/8/7
Y1 - 2009/8/7
N2 - Human breast tumors contain a breast cancer stem cell (BCSC) population with properties reminiscent of normal stem cells. We found 37 microRNAs that were differentially expressed between human BCSCs and nontumorigenic cancer cells. Three clusters, miR-200c-141, miR-200b-200a-429, and miR-183-96-182 were downregulated in human BCSCs, normal human and murine mammary stem/progenitor cells, and embryonal carcinoma cells. Expression of BMI1, a known regulator of stem cell self-renewal, was modulated by miR-200c. miR-200c inhibited the clonal expansion of breast cancer cells and suppressed the growth of embryonal carcinoma cells in vitro. Most importantly, miR-200c strongly suppressed the ability of normal mammary stem cells to form mammary ducts and tumor formation driven by human BCSCs in vivo. The coordinated downregulation of three microRNA clusters and the similar functional regulation of clonal expansion by miR-200c provide a molecular link that connects BCSCs with normal stem cells.
AB - Human breast tumors contain a breast cancer stem cell (BCSC) population with properties reminiscent of normal stem cells. We found 37 microRNAs that were differentially expressed between human BCSCs and nontumorigenic cancer cells. Three clusters, miR-200c-141, miR-200b-200a-429, and miR-183-96-182 were downregulated in human BCSCs, normal human and murine mammary stem/progenitor cells, and embryonal carcinoma cells. Expression of BMI1, a known regulator of stem cell self-renewal, was modulated by miR-200c. miR-200c inhibited the clonal expansion of breast cancer cells and suppressed the growth of embryonal carcinoma cells in vitro. Most importantly, miR-200c strongly suppressed the ability of normal mammary stem cells to form mammary ducts and tumor formation driven by human BCSCs in vivo. The coordinated downregulation of three microRNA clusters and the similar functional regulation of clonal expansion by miR-200c provide a molecular link that connects BCSCs with normal stem cells.
UR - http://www.scopus.com/inward/record.url?scp=68049114782&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=68049114782&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2009.07.011
DO - 10.1016/j.cell.2009.07.011
M3 - Article
C2 - 19665978
AN - SCOPUS:68049114782
SN - 0092-8674
VL - 138
SP - 592
EP - 603
JO - Cell
JF - Cell
IS - 3
ER -
