Downregulation of miRNA-200c Links Breast Cancer Stem Cells with Normal Stem Cells

Yohei Shimono, Maider Zabala, Robert W. Cho, Neethan Lobo, Piero Dalerba, Dalong Qian, Maximilian Diehn, Huiping Liu, Sarita P. Panula, Eric Chiao, Frederick M. Dirbas, George Somlo, Renee A Reijo Pera, Kaiqin Lao, Michael F. Clarke*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

941 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)592-603
Number of pages12
JournalCell
Volume138
Issue number3
DOIs
StatePublished - Aug 7 2009

Keywords

  • HUMDISEASE
  • STEMCELL

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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